Cyclobutanecarbonyl chloride → Cyclobutanecarboxylic acid {(1S,2R,3S,4R)-4-[2-chloro-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl}-amide

HRID 1882512Notes

Reaction equation

HRID 1882512 reaction equation
Cl.[NH2:2][C@H:3]1[CH2:7][C@@H:6]([N:8]2[CH:16]=[N:15][C:14]3[C:9]2=[N:10][C:11]([Cl:32])=[N:12][C:13]=3[NH:17][CH2:18][CH:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C@H:5]([OH:33])[C@@H:4]1[OH:34].C(N(C(C)C)CC)(C)C.[CH:44]1([C:48](Cl)=[O:49])[CH2:47][CH2:46][CH2:45]1>C1COCC1>[Cl:32][C:11]1[N:10]=[C:9]2[C:14]([N:15]=[CH:16][N:8]2[C@@H:6]2[CH2:7][C@H:3]([NH:2][C:48]([CH:44]3[CH2:47][CH2:46][CH2:45]3)=[O:49])[C@@H:4]([OH:34])[C@H:5]2[OH:33])=[C:13]([NH:17][CH2:18][CH:19]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:12]=1

Participants

5

Reactant 3

HCID 78705Cyclobutanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 86622640(1S,2R,3S,5R)-3-Amino-5-[2-chloro-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-cyclopentane-1,2-diol hydrochloride

Product 1

HCID 86622641Cyclobutanecarboxylic acid {(1S,2R,3S,4R)-4-[2-chloro-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl}-amideYield 46.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (1S,2R,3S,5R)-3-amino-5-[2-chloro-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-cyclopentane-1,2-diol hydrochloride (Intermediate JJ3) (100 mg, 0.2 mmol) in dry THF (1 ml) is treated with diisopropylethylamine (0.17 ml, 1 mmol) and cyclobutanecarboxylic acid chloride (0.023 ml, 0.2 mmol) and the mixture is stirred at room temperature for 48 hours. The solvent is removed under reduced pressure. The residue is purified by reverse-phase chromatography eluting with a gradient system of acetonitrile (0.1% TFA): water (0.1% TFA) (0:100 by volume) gradually changing to acetonitrile (0.1% TFA): water (0.1% TFA) (100:0 by volume) to afford the title compound (51 mg). LCMS (electrospray): m/z [MH+] 547.26. 1H nmr (MeOD, 400 MHz); 8.00 (s, 1H), 7.40-7.25 (m, 8H), 7.20-7.15 (m, 2H), 4.70 (m, 1H), 4.50 (m, 2H), 4.20 (m, 2H), 3.95 (m, 1H), 2.85 (m, 1H), 2.30 (m, 2H), 2.20 (m, 2H), 2.05 (m, 2H), 1.90 (m, 1H).

Workup

  1. customThe solvent is removed under reduced pressure
  2. customThe residue is purified by reverse-phase chromatography
  3. washeluting with a gradient system of acetonitrile (0.1% TFA)

Sources & evidence

ORD record
ord-1c3017b430944884832a2ab7d90a4af5
Source dataset
uspto-grants-2012_11
Patent number
US08318750B2

Reaction notes

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