Water → tert-butyl 3-[({4-[(1-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-4-yl)amino]quinazolin-7-yl}oxy)methyl]pyrrolidine-1-carboxylate

HRID 640001Notes

Reaction equation

HRID 640001 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:28])[CH2:10][N:11]2[CH:15]=[C:14]([NH:16][C:17]3[C:26]4[C:21](=[CH:22][C:23]([OH:27])=[CH:24][CH:25]=4)[N:20]=[CH:19][N:18]=3)[CH:13]=[N:12]2)[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(O[CH2:40][CH:41]1[CH2:45][CH2:44][N:43]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:42]1)(=O)=O.O>CC(N(C)C)=O>[F:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:28])[CH2:10][N:11]2[CH:15]=[C:14]([NH:16][C:17]3[C:26]4[C:21](=[CH:22][C:23]([O:27][CH2:40][CH:41]5[CH2:45][CH2:44][N:43]([C:46]([O:48][C:49]([CH3:50])([CH3:52])[CH3:51])=[O:47])[CH2:42]5)=[CH:24][CH:25]=4)[N:20]=[CH:19][N:18]=3)[CH:13]=[N:12]2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 4183641tert-Butyl 3-(((methylsulfonyl)oxy)methyl)pyrrolidine-1-carboxylateHCID 136383490N-(3-fluorophenyl)-2-{4-[(7-hydroxyquinazolin-4-yl)amino]-1H-pyrazol-1-yl}acetamide

Product 1

HCID 68638512tert-butyl 3-[({4-[(1-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-4-yl)amino]quinazolin-7-yl}oxy)methyl]pyrrolidine-1-carboxylateYield 65%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of N-(3-fluorophenyl)-2-{4-[(7-hydroxyquinazolin-4-yl)amino]-1H-pyrazol-1-yl}acetamide (0.59 g, 1.2 mmol), cesium carbonate (1.95 g, 6.0 mmol) and tert-butyl 3-{[(methylsulphonyl)oxy]methyl}pyrrolidine-1-carboxylate (assumed 1.3 mmol) in dimethyl acetamide (10 ml) was heated at 80° C. for 6 hours. The mixture was poured into water and extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over magnesium sulphate and evaporated in vacuo. The residue was purified by silica gel chromatography eluting with 4 to 7% methanol in dichloromethane to yield tert-butyl 3-[({4-[(1-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-4-yl)amino]quinazolin-7-yl}oxy)methyl]pyrrolidine-1-carboxylate (0.435 g, 65% yield): MS (+ve ESI): 562 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over magnesium sulphate
  5. customevaporated in vacuo
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with 4 to 7% methanol in dichloromethane

Sources & evidence

ORD record
ord-125644f320df4bad9429967237e8d12c
Source dataset
uspto-grants-2010_04
Patent number
US07691867B2

Reaction notes

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