Triethylamine → Acetic acid 1,1-dimethyl-2-{3-[9-methyl-2-(2-methylbenzoimidazol-1-yl)-6-morpholin-4-yl-9H-purin-8-ylmethyl]azetidin-1-yl}-2-oxoethyl ester

HRID 1922848

Reaction equation

HRID 1922848 reaction equation
[NH:1]1[CH2:4][CH:3]([CH2:5][C:6]2[N:7]([CH3:33])[C:8]3[C:13]([N:14]=2)=[C:12]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[N:11]=[C:10]([N:21]2[C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=4[N:23]=[C:22]2[CH:30](C)C)[N:9]=3)[CH2:2]1.Cl[C:35]([C:37]([O:40][C:41](=[O:43])[CH3:42])([CH3:39])[CH3:38])=[O:36].CCN(CC)CC>C1COCC1>[CH3:38][C:37]([O:40][C:41](=[O:43])[CH3:42])([CH3:39])[C:35]([N:1]1[CH2:2][CH:3]([CH2:5][C:6]2[N:7]([CH3:33])[C:8]3[C:13]([N:14]=2)=[C:12]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[N:11]=[C:10]([N:21]2[C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=4[N:23]=[C:22]2[CH3:30])[N:9]=3)[CH2:4]1)=[O:36]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1234962-Acetoxyisobutyroyl chlorideHCID 596056358-Azetidin-3-ylmethyl-2-(2-isopropylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine

Product 1

HCID 59606028Acetic acid 1,1-dimethyl-2-{3-[9-methyl-2-(2-methylbenzoimidazol-1-yl)-6-morpholin-4-yl-9H-purin-8-ylmethyl]azetidin-1-yl}-2-oxoethyl esterYield 80.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 8-azetidin-3-ylmethyl-2-(2-isopropylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine (100 mg, 0.22 mmol), acetic acid 1-chlorocarbonyl-1-methylethyl ester (32 μL, 0.22 mmol) and NEt3 (29 μL, 0.22 mmol) in THF (3 mL) was allowed to stir at r.t. for 16 h then concentrated in vacuo. The resulting residue was partitioned between DCM and H2O, the organic phase dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-7%) affording the title compound as a white foam (97 mg, 75%)._LCMS (method A): RT 2.65 min [M+H]+ 575.3

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe resulting residue was partitioned between DCM and H2O
  3. dry with materialthe organic phase dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-7%)

Sources & evidence

ORD record
ord-ab8351f3031343d0a6613bb8f88faf6e
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Linked notes

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