Potassium Carbonate → HCID 86604092, compound

HRID 2102444Notes

Reaction equation

HRID 2102444 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[C:10]([F:30])=[C:11]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([OH:29])=[C:24]([O:27][CH3:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:12]=[CH:13][C:14]=1[Cl:15].CS(OC[CH:37]1[CH2:51][C@@H:40]2[CH2:41][N:42]([C:44]([O:46][C:47](C)(C)C)=[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>[CH2:41]1[CH:40]2[CH2:51][CH2:37][CH2:38][CH:39]2[CH2:43][N:42]1[C:44]([O:46][CH2:47][O:29][C:23]1[CH:22]=[C:21]2[C:26]([C:17]([NH:16][C:11]3[CH:12]=[CH:13][C:14]([Cl:15])=[C:9]([Cl:8])[C:10]=3[F:30])=[N:18][CH:19]=[N:20]2)=[CH:25][C:24]=1[O:27][CH3:28])=[O:45]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 86604091tert-butyl (3aR,5r,6aS)-5-(((methylsulfonyl)oxy)methyl)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylateHCID 136335142HCID 136335142, compound

Product 1

HCID 86604092HCID 86604092, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

A solution of 4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-ol trifluoroacetate (salt) (0.22 g, 0.47 mmol), 1,1-dimethylethyl (3aR,6aS)-5-{[(methylsulfonyl)oxy]methyl}hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (0.16 g, 0.51 mmol), K2CO3 (0.33 g, 2.36 mmol) in N,N-dimethylacetamide (5 mL) was heated in a sealed reaction tube at 90° C. for 12 h. The crude reaction mixture was diluted with 100 mL 10% methanol in ethyl acetate and washed with saturated aqueous sodium bicarbonate (1×30 mL), water (1×30 mL) and brine (1×30 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Column chromatography (SiO2, 3:2 hexanes:acetone) provided 1,1-dimethylethyl (3aR,6aS)-5-({[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxymethyl) hexahydrocyclopenta-[c]pyrrole-2(1H)-carboxylate which was used directly in the next step. MS (EI) for C28H31Cl2FN4O4: 577, 579 (MH+).

Workup

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

Sources & evidence

ORD record
ord-9cc45868e9fa4f32bc5436adb9645d75
Source dataset
uspto-grants-2009_08
Patent number
US07576074B2

Reaction notes

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