Dimethylformamide → 6-Chloro famciclovir

HRID 1461512Notes

Reaction equation

HRID 1461512 reaction equation
[C:1]([O:4][CH2:5][CH:6]([CH2:10][CH2:11]CCBr)[C:7]([O-:9])=O)(=[O:3])[CH3:2].[NH2:15][C:16]1[N:24]=[C:23]2[C:19]([NH:20][CH:21]=[N:22]2)=[C:18]([Cl:25])[N:17]=1.[C:26](=[O:29])([O-])[O-].[K+].[K+].[CH3:32]N(C)C=O>>[C:26]([O:9][CH2:7][CH:6]([CH2:5][O:4][C:1](=[O:3])[CH3:2])[CH2:10][CH2:11][N:22]1[CH:21]=[N:20][C:19]2[C:23]1=[N:24][C:16]([NH2:15])=[N:17][C:18]=2[Cl:25])(=[O:29])[CH3:32]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 53603492-Amino-6-chloropurineHCID 867453192-Acetoxymethyl-4-bromobut-1-yl-acetate

Product 1

HCID 101551646-Chloro famciclovirYield 80%

Procedure

A mixture of 2-acetoxymethyl-4-bromobut-1-yl-acetate (13.0 g, 48.7 mmol), 2-amino-6-chloro-purine (8.25 g, 48.7 mmol) and anhydrous potassium carbonate (10 g, 72.5 mmol) was stirred in dry dimethylformamide (100 ml) for 18 hours at room temperature. The reaction mixture was then filtered, the filtrate evaporated, and the residue purified by column chromatography on silica gel (500 g). Elution with 3% methanol in chloroform afforded 9-(4-acetoxy-3-acetoxymethyl-but-1-yl)-2-amino-6-chloropurine as a white solid (13.8 g, 80%) mp 135°-137°. λmax (H2 0) 222 (ε28,500), 245 (ε4,800) 307 (ε7,700) nm; νmax (KBr)3485, 3310, 3200, 1750, 1730, 1625, 1560, 1525, 1475, 1245 cm-1. δH [(CD3)2SO] (270 MHz) 1.85-2.05 (3 H, m, CHCH2CH2), 2.01 (6 H, s, 2×OCOCH3), 4.03 (4 H, d, 2×CH2OCOCH3), 4.16 (2 H, t, CH2N), 6.88 (2 H, br s, D2O exchangeable, NH2), 8.17 (1 H, s, 8-H). Found C, 47.27; H, 4.94; N, 19.56%. C14H18N5O4Cl requires C, 47.26; H, 5.10; N 19.68%.

Workup

  1. filtrationThe reaction mixture was then filtered
  2. customthe filtrate evaporated
  3. customthe residue purified by column chromatography on silica gel (500 g)
  4. washElution with 3% methanol in chloroform

Sources & evidence

ORD record
ord-bb5d263d4cd945f499cfccbb9828f04b
Source dataset
uspto-grants-1991_12
Patent number
US05075445

Reaction notes

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