Potassium Carbonate → 9-(2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

HRID 1922782Notes

Reaction equation

HRID 1922782 reaction equation
Br[CH2:2][C:3]1[S:11][C:10]2[C:9]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=[N:8][C:7]([Cl:18])=[N:6][C:5]=2[CH:4]=1.[O:19]1[C:24]2([CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[CH2:23][NH:22][C:21](=[O:30])[CH2:20]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:18][C:7]1[N:8]=[C:9]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:10]2[S:11][C:3]([CH2:2][N:27]3[CH2:26][CH2:25][C:24]4([O:19][CH2:20][C:21](=[O:30])[NH:22][CH2:23]4)[CH2:29][CH2:28]3)=[CH:4][C:5]=2[N:6]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 130594341-Oxa-4,9-diazaspiro(5.5)undecan-3-oneHCID 461807264-(6-(Bromomethyl)-2-chlorothieno[3,2-d]pyrimidin-4-yl)morpholine

Product 1

HCID 596035099-(2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-oneYield 82.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 6-bromomethyl-2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (500 mg, 1.43 mmol), 1-oxa-4,9-diaza-spiro[5.5]undecan-3-one (315 mg, 1.85 mmol) and potassium carbonate (450 mg, 3.26 mmol) in DMF (40 mL) was stirred at ambient temperature for 18 hours, then loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was washed with MeOH and the desired product was subsequently eluted using 2 M NH3 in MeOH. The eluent was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH 100:0 to 98:2 to 95:5) to afford 9-(2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one as a white solid (515 mg, 82%). LCMS (Method A): RT=2.51 min, [M+H]+ 438.1

Workup

  1. washThe cartridge was washed with MeOH
  2. washthe desired product was subsequently eluted
  3. customThe eluent was collected
  4. concentrationconcentrated in vacuo
  5. customThe resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH 100:0 to 98:2 to 95:5)

Sources & evidence

ORD record
ord-6562797ea0104dc89f772543bc916f22
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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