Triphenylphosphine → 1-({2-(Hex-5-enyl-methyl-carbamoyl)-4-[2-(3-isopropyl-pyrazol-1-yl)-7-methoxy-8-methyl-quinazolin-4-yloxy]-cyclopentanecarbonyl}-amino)-2-vinyl-cyclopropane-carboxylic acid ethyl ester

HRID 1443494Notes

Reaction equation

HRID 1443494 reaction equation
CC(OC(/N=N/C(OC(C)C)=O)=O)C.[CH2:15]([O:17][C:18]([C:20]1([NH:25][C:26]([CH:28]2[CH2:32][CH:31]([OH:33])[CH2:30][CH:29]2[C:34](=[O:43])[N:35]([CH2:37][CH2:38][CH2:39][CH2:40][CH:41]=[CH2:42])[CH3:36])=[O:27])[CH2:22][CH:21]1[CH:23]=[CH2:24])=[O:19])[CH3:16].O[C:45]1[C:54]2[C:49](=[C:50]([CH3:57])[C:51]([O:55][CH3:56])=[CH:52][CH:53]=2)[N:48]=[C:47]([N:58]2[CH:62]=[CH:61][C:60]([CH:63]([CH3:65])[CH3:64])=[N:59]2)[N:46]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C>[CH2:15]([O:17][C:18]([C:20]1([NH:25][C:26]([CH:28]2[CH2:32][CH:31]([O:33][C:45]3[C:54]4[C:49](=[C:50]([CH3:57])[C:51]([O:55][CH3:56])=[CH:52][CH:53]=4)[N:48]=[C:47]([N:58]4[CH:62]=[CH:61][C:60]([CH:63]([CH3:65])[CH3:64])=[N:59]4)[N:46]=3)[CH2:30][CH:29]2[C:34](=[O:43])[N:35]([CH2:37][CH2:38][CH2:39][CH2:40][CH:41]=[CH2:42])[CH3:36])=[O:27])[CH2:22][CH:21]1[CH:23]=[CH2:24])=[O:19])[CH3:16]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 668706071-{[2-(Hex-5-enyl-methyl-carbamoyl)-4-hydroxy-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl esterHCID 1784877607-methoxy-8-methyl-2-(3-propan-2-ylpyrazol-1-yl)-1H-quinazolin-4-one

Product 1

HCID 686895471-({2-(Hex-5-enyl-methyl-carbamoyl)-4-[2-(3-isopropyl-pyrazol-1-yl)-7-methoxy-8-methyl-quinazolin-4-yloxy]-cyclopentanecarbonyl}-amino)-2-vinyl-cyclopropane-carboxylic acid ethyl esterYield 37.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIAD (280 μL, 1.42 mmol) was added at −20° C. under nitrogen atmosphere to a solution of the alcohol (143) (367 mg, 0.90 mmol), 4-hydroxy-2-(3-isopropylpyrazol-1-yl)-7-methoxy-8-methylquinazoline (141) (270 mg, 0.90 mmol) and triphenyl-phosphine (288 mg, 1.42 mmol) in dry DMF (35 mL). After 2 h, the solution was warmed up to room temperature. After 12 h, the reaction mixture was partitioned between ice-cold water and ether, organic layer was dried (Na2SO4) and evaporated. The residue was purified by column chromatography (gradient AcOEt/CH2Cl2, 1:9 to 10:0) to give the title compound (230 mg, 34%), m/z=687 (M+H)+.

Workup

  1. waitAfter 12 h
  2. customthe reaction mixture was partitioned between ice-cold water and ether, organic layer
  3. dry with materialwas dried (Na2SO4)
  4. customevaporated
  5. customThe residue was purified by column chromatography (gradient AcOEt/CH2Cl2, 1:9 to 10:0)

Sources & evidence

ORD record
ord-c04dad73a2db41489193bd369e6f252f
Source dataset
uspto-grants-2010_02
Patent number
US07659245B2

Reaction notes

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