Potassium Carbonate → tert-butyl 5-(3-((4-((4-bromo-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate

HRID 712524Notes

Reaction equation

HRID 712524 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:24][CH3:25])=[C:16]([O:19][CH2:20][CH2:21][CH2:22]Cl)[CH:17]=3)[N:12]=[CH:11][N:10]=2)=[C:4]([F:26])[CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH2:33]1[CH:37]2[CH2:38][NH:39][CH2:40][CH:36]2[CH2:35][N:34]1[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42]>CN(C=O)C.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:24][CH3:25])=[C:16]([O:19][CH2:20][CH2:21][CH2:22][N:39]4[CH2:38][CH:37]5[CH2:33][N:34]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:35][CH:36]5[CH2:40]4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)=[C:4]([F:26])[CH:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 4142526Tert-butyl octahydropyrrolo(3,4-c)pyrrole-2-carboxylateHCID 86729473HCID 86729473, compound

Product 1

HCID 86729522tert-butyl 5-(3-((4-((4-bromo-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylateYield 66.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of N-(4-bromo-2-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine (1.25 g), K2CO3 (0.78 g) and a catalytic amount of KI in DMF (20 mL) was added tert-butyl hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (0.78 g) at room temperature. The reaction mixture was heated to 80° C. and stirred for 8 h, then diluted with water and extracted with CH2Cl2. The organic layer was dried over anhydrous Na2SO4 for 1 h and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 30:1 (v/v) DCM/MeOH) to give the title compound as a white solid (1.16 g, 66.50%).

Workup

  1. extractionextracted with CH2Cl2
  2. dry with materialThe organic layer was dried over anhydrous Na2SO4 for 1 h
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue was chromatographed with a silica gel column (eluting agent: 30:1 (v/v) DCM/MeOH)

Sources & evidence

ORD record
ord-83a7914a426e447fbcca6efe5209c74a
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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