Potassium Carbonate → HCID 66838628, compound

HRID 244544Notes

Reaction equation

HRID 244544 reaction equation
FC(F)(F)C(O)=O.[Br:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([OH:28])=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[C:11]([F:29])[C:10]=1[Cl:30].CS(O[CH2:36][CH:37]1[CH2:51][C@@H:40]2[CH2:41][N:42]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:43][C@@H:39]2[CH2:38]1)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>CN(C)C(=O)C.CO.C(OCC)(=O)C>[Br:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:28][CH2:36][CH:37]4[CH2:51][C@@H:40]5[CH2:41][N:42]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:43][C@@H:39]5[CH2:38]4)=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[C:11]([F:29])[C:10]=1[Cl:30]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 86604091tert-butyl (3aR,5r,6aS)-5-(((methylsulfonyl)oxy)methyl)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylateHCID 136335145HCID 136335145, compound

Product 1

HCID 66838628HCID 66838628, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

A solution of 4-[(4-bromo-3-chloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-ol trifluoroacetate (salt) (0.217 g, 0.425 mmol), 1,1-dimethylethyl (3aR,6aS)-5-{[(methylsulfonyl)oxy]methyl}hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (0.163 g, 0.510 mmol), potassium carbonate (0.290 g, 2.12 mmol) in N,N-dimethylacetamide (1.6 mL) was heated in a sealed reaction tube at 90° C. for 12 h. The crude reaction mixture was diluted with 100 mL of 10% methanol in ethyl acetate and washed with water (5×30 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Column chromatography (SiO2, 3:1 hexanes:acetone) provided 1,1-dimethylethyl (3aR,6aS)-5-({[4-[(4-bromo-3-chloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate which was used directly in the next step. MS (EI) for C28H31N4O4FClBr: 623 (MH+).

Workup

  1. customThe crude reaction mixture
  2. washwashed with water (5×30 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c4280fba4d434a948402f30b4084042c
Source dataset
uspto-grants-2014_02
Patent number
US08658654B2

Reaction notes

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