Diisopropylamine → 3-[5-(2-Ethylbenzoimidazol-1-yl)-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethylene]azetidine-1-carboxylic acid tert-butyl ester

HRID 1922772Notes

Reaction equation

HRID 1922772 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.COP([CH2:19][C:20]1[S:21][C:22]2[N:23]=[C:24]([N:35]3[C:39]4[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=4[N:37]=[C:36]3[CH2:44][CH3:45])[N:25]=[C:26]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)[C:27]=2[N:28]=1)(=O)OC.[C:46]([O:50][C:51]([N:53]1[CH2:56][C:55](=O)[CH2:54]1)=[O:52])([CH3:49])([CH3:48])[CH3:47]>C1COCC1>[C:46]([O:50][C:51]([N:53]1[CH2:56][C:55](=[CH:19][C:20]2[S:21][C:22]3[N:23]=[C:24]([N:35]4[C:39]5[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=5[N:37]=[C:36]4[CH2:44][CH3:45])[N:25]=[C:26]([N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)[C:27]=3[N:28]=2)[CH2:54]1)=[O:52])([CH3:49])([CH3:47])[CH3:48]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 59606043[5-(2-Ethylbenzoimidazol-1-yl)-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethyl]phosphonic acid dimethyl esterHCID 178418339Butyllithium

Product 1

HCID 596056233-[5-(2-Ethylbenzoimidazol-1-yl)-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethylene]azetidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of diisopropylamine (200 μL, 1.42 mmol) in THF (0.5 mL) at −78° C. was added n-BuLi (556 μL, 1.42 mmol, 2.5 M in hexanes) and the resulting mixture stirred for 20 min. The resulting solution was added to a suspension of [5-(2-ethylbenzoimidazol-1-yl)-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethyl]phosphonic acid dimethyl ester (620 mg, 1.27 mmol) in THF (11 mL) at −78° C. The resulting mixture was warmed to r.t. before a solution of 3-oxo-azetidine-1-carboxylic acid tert-butyl ester (250 mg, 1.46 mmol) in THF (1.5 mL) was added. The resulting mixture was stirred at r.t. for 5 h then quenched with H2O. The mixture was concentrated in vacuo and the residue was partitioned between DCM and brine. The organic phase was dried (MgSO4) and concentrated in vacuo. The resulting residue was filtered through a pad of silica affording the title compound (493 mg, 73%). LCMS (method H): RT 3.72 min, [M+H]+ 534.3

Workup

  1. additionwas added
  2. stirringThe resulting mixture was stirred at r.t. for 5 h
  3. customthen quenched with H2O
  4. concentrationThe mixture was concentrated in vacuo
  5. customthe residue was partitioned between DCM and brine
  6. dry with materialThe organic phase was dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. filtrationThe resulting residue was filtered through a pad of silica affording the title compound (493 mg, 73%)
  9. customRT 3.72 min, [M+H]+ 534.3

Sources & evidence

ORD record
ord-221d43d504f349c79d9e4089923be5e2
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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