Water → Tert-butyl 1-allyl-4-{[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methyl}piperazine-2-carboxylate

HRID 394104Notes

Reaction equation

HRID 394104 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:17]=[C:16]([CH2:18][N:19]2[CH2:24][CH2:23][N:22]([C:25](OCC=C)=O)[CH:21]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:20]2)[CH:15]=[C:14]2[C:9]=1[CH2:10][NH:11][C:12](=[O:46])[N:13]2[C:38]1[C:43]([Cl:44])=[CH:42][CH:41]=[CH:40][C:39]=1[Cl:45].O.[CH2:48]([SnH](CCCC)CCCC)[CH2:49]CC>C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:17]=[C:16]([CH2:18][N:19]2[CH2:24][CH2:23][NH:22][CH:21]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:20]2)[CH:15]=[C:14]2[C:9]=1[CH2:10][NH:11][C:12](=[O:46])[N:13]2[C:38]1[C:43]([Cl:44])=[CH:42][CH:41]=[CH:40][C:39]=1[Cl:45].[CH2:25]([N:22]1[CH2:23][CH2:24][N:19]([CH2:18][C:16]2[CH:15]=[C:14]3[C:9]([CH2:10][NH:11][C:12](=[O:46])[N:13]3[C:38]3[C:43]([Cl:44])=[CH:42][CH:41]=[CH:40][C:39]=3[Cl:45])=[C:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])[CH:17]=2)[CH2:20][CH:21]1[C:31]([O:33][C:34]([CH3:35])([CH3:36])[CH3:37])=[O:32])[CH:48]=[CH2:49]

Participants

7

Reactant 3

HCID 962WaterHCID 5948TributylstannaneHCID 698511001-Allyl 2-tert-butyl 4-{[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methyl}piperazine-1,2-dicarboxylate

Product 2

HCID 10282953Tert-butyl 1-allyl-4-{[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methyl}piperazine-2-carboxylateHCID 22648143Tert-butyl 4-{[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methyl}piperazine-2-carboxylate

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 1-allyl 2-tert-butyl 4-{[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methyl}piperazine-1,2-dicarboxylate (EXAMPLE AAA10, STEP A, 200 mg, 0.29 mmol) and dichlorobis(triphenylphosphine)palladium(II) (10.2 mg, 0.0146 mL) in methylene chloride (3 mL) was added water (30 μL). To this mixture was added tributyltin hydride (94 μL, 0.348 mmol) rapidly. The mixture was stirred at rt for 5 h, diluted with methylene chloride, washed with water and brine, and dried over anhydrous sodium sulfate. Removal of the solvent and subsequent purification by preparative thin layer chromatography using 5% of 2N ammonium in methanol/methylene chloride as eluent provided tert-butyl 4-{[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methyl}piperazine-2-carboxylate and tert-butyl 1-allyl-4-{[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methyl}piperazine-2-carboxylate.

Workup

  1. washwashed with water and brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. customRemoval of the solvent and subsequent purification by preparative thin layer chromatography

Sources & evidence

ORD record
ord-00d29a8c85d740e6be460d905940a601
Source dataset
uspto-grants-2004_10
Patent number
US06809199B2

Reaction notes

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