Propionyl chloride → N-[(1S,2R,3S,4R)-4-[2-Chloro-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl]-propionamide

HRID 2382358Notes

Reaction equation

HRID 2382358 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C@H:9]1[CH2:13][C@@H:12]([N:14]2[CH:22]=[N:21][C:20]3[C:15]2=[N:16][C:17]([Cl:38])=[N:18][C:19]=3[NH:23][CH2:24][CH:25]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@H:11]([OH:39])[C@@H:10]1[OH:40].C(N(C(C)C)CC)(C)C.[C:50](Cl)(=[O:53])[CH2:51][CH3:52]>C1COCC1>[Cl:38][C:17]1[N:16]=[C:15]2[C:20]([N:21]=[CH:22][N:14]2[C@@H:12]2[CH2:13][C@H:9]([NH:8][C:50](=[O:53])[CH2:51][CH3:52])[C@@H:10]([OH:40])[C@H:11]2[OH:39])=[C:19]([NH:23][CH2:24][CH:25]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:18]=1

Participants

5

Reactant 3

HCID 62324Propionyl chlorideHCID 81531DiisopropylethylamineHCID 86622631(1S,2R,3S,5R)-3-Amino-5-[2-chloro-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-cyclopentane-1,2-diol trifluoroacetate

Product 1

HCID 86622630N-[(1S,2R,3S,4R)-4-[2-Chloro-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl]-propionamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(1S,2R,3S,5R)-3-Amino-5-[2-chloro-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-cyclopentane-1,2-diol trifluoroacetate (9.50 g, 16.42 mmol) and diisopropylethylamine (6.36 g, 49.27 mmol) are placed in a flask with dry THF (150 ml). Propionyl chloride (1.52 g, 16.42 mmol) is added dropwise and the reaction mixture is stirred at room temperature. The reaction is shown to be complete by LCMS after 1 hour. The solvent is removed in vacuo and the residue is partitioned between dichloromethane (250 ml) and water (250 ml). The organic layer is washed with water (200 ml) and brine (200 ml), dried over MgSO4, filtered and the solvent is removed in vacuo. The solid is recrystallised from 1,2-dichloroethane to give the title compound. 1H nmr (MeOD, 400 MHz); 8.00 (s, 1H), 7.40-7.15 (m, 10H), 4.75 (m, 1H), 4.60 (m, 1H), 4.50 (m, 1H), 4.20 (m, 3H), 3.95 (m, 1H), 2.85 (m, 1H), 2.40 (q, 2H), 2.10 (m, 1H), 1.20 (t, 3H), MS (ES+) m/e 521 (MH+).

Workup

  1. customThe solvent is removed in vacuo
  2. customthe residue is partitioned between dichloromethane (250 ml) and water (250 ml)
  3. washThe organic layer is washed with water (200 ml) and brine (200 ml)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customthe solvent is removed in vacuo
  7. customThe solid is recrystallised from 1,2-dichloroethane

Sources & evidence

ORD record
ord-2e655d119f114bbebc384ca9c61abdb6
Source dataset
uspto-grants-2012_09
Patent number
US08258141B2

Reaction notes

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