Chemistry Reference
In-Depth Information
H
2
N
1382
O
N
O
CN
O
O
NH
2
SH
- NH
3
S
COCl
2
88 %
99,5 %
1380
1381
1383
toluene (200 mL) and dichloromethane (50 mL) and the solution was cooled in an
ice bath. A 12% solution of phosgene in toluene (for a safe source, see Chapter 7)
(100.0 mL; 0.13 mol) was added dropwise at such a rate as to keep the temperature
below 10
C. The reaction mixture was then allowed to warm to room temperature
and water (50 mL) was added. The organic layer was washed with dilute aq. HCl
and water, dried, and concentrated to yield 15.1 g (0.085 mol, 88%) of 1381 as an
oil.
2-(2,3,5-Tri-O-acetyl-b-d-ribofuranosyl)-1,2,3-triazole-4,5-dicarbonitrile 1386,an
analogue of the human myeloid leukemia cell growth inhibitor Ribavirin 1384, has
been prepared from its carboxamide 1385 by dehydration with phosgene [1050].
O
H
2
NOC
CONH
2
NC
CN
H
2
N
N
N
N
N
N
N
H
N
AcO
N
AcO
N
O
O
O
COCl
2
CH
2
Cl
2
0°C, 2 h
OAcOAc
OH
OH
OAcOAc
90 %
Ribavirin
1384
1385
1386
Typical procedure. 2-(2,3,5-Tri-O-acetyl-b-
d
-ribofuranosyl)-1,2,3-triazole-4,5-dicarbonitrile
1386 [1050]:
To a cold (
5
C) solution of carboxamide 1385 (4.7 g, 11.4 mmol) in
anhydrous dichloromethane (75 mL) and pyridine (10 mL), a solution of 20%
phosgene in toluene (for a safe source, see Chapter 7) (14.7 mL, 30 mmol) was
added dropwise with stirring. After the addition was complete (30 min), the reac-
tion mixture was stirred at 0
C for 2 h. The resulting brown solution was poured
onto crushed ice (200 g) and extracted with dichloromethane (3
100 mL). The
combined organic layers were washed successively with cold 1 n HCl (10 mL), 10%
aqueous NaHCO
3
(2
50 mL), and then dried (Na
2
SO
4
)
and concentrated to dryness. Crystallization of the residue from EtOH furnished
3.9 g (90%) of 2-(2,3,5-tri-O-acetyl-b-d-ribofuranosyl)-1,2,3-triazole-4,5-dicarbonitrile
1386; mp 121
C.
2,3-Dicyanopyridine has been prepared from the corresponding quinolinic acid
diamide with phosgene in 64% yield [1051]. Asparagine and glutamine react with
100 mL), and water (2
