3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → 3-(2-Chloro-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-ylmethylene)azetidine-1-carboxylic acid tert-butyl ester

HRID 1945622Notes

Reaction equation

HRID 1945622 reaction equation
COP([CH2:7][C:8]1[S:16][C:15]2[C:14]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[N:13][C:12]([Cl:23])=[N:11][C:10]=2[CH:9]=1)(=O)OC.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:34]([O:38][C:39]([N:41]1[CH2:44][C:43](=O)[CH2:42]1)=[O:40])([CH3:37])([CH3:36])[CH3:35]>C1COCC1>[C:34]([O:38][C:39]([N:41]1[CH2:44][C:43](=[CH:7][C:8]2[S:16][C:15]3[C:14]([N:17]4[CH2:18][CH2:19][O:20][CH2:21][CH2:22]4)=[N:13][C:12]([Cl:23])=[N:11][C:10]=3[CH:9]=2)[CH2:42]1)=[O:40])([CH3:37])([CH3:35])[CH3:36]

Participants

5

Reactant 3

HCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 2733832Lithium HexamethyldisilazideHCID 86618396(2-Chloro-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-ylmethyl)phosphonic acid dimethyl ester

Product 1

HCID 596057503-(2-Chloro-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-ylmethylene)azetidine-1-carboxylic acid tert-butyl esterYield 63.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of (2-chloro-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-ylmethyl)phosphonic acid dimethyl ester (3.0 g, 7.94 mmol) in THF (150 mL) at −78° C. was added LiHMDS (8.8 mL, 8.80 mmol, 1M solution in THF) and the resulting mixture stirred for 30 min then warmed to r.t. before the addition of a solution of 3-oxo-azetidine-1-carboxylic acid tert-butyl ester (1.51 g, 8.82 mmol) in THF (20 mL). The reaction mixture was stirred at r.t. for 16 h then quenched with H2O and MeOH and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:DCM, 5-100%) affording the title compound as a yellow solid (2.14 g, 63%). LCMS (method A): RT 3.97 min [M+H]+ 423.3

Workup

  1. stirringThe reaction mixture was stirred at r.t. for 16 h
  2. customthen quenched with H2O and MeOH
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified by column chromatography (Si—PCC, EtOAc:DCM, 5-100%)

Sources & evidence

ORD record
ord-ecae611a1406418cad323ef8b7885758
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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