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

HRID 394106Notes

Reaction equation

HRID 394106 reaction equation
C([N:4]1[CH2:9][CH2:8][N:7]([CH2:10][C:11]2[CH:20]=[C:19]3[C:14]([CH2:15][NH:16][C:17](=[O:29])[N:18]3[C:21]3[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][C:22]=3[Cl:28])=[C:13]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[Cl:36])[CH:12]=2)[CH2:6][CH:5]1[C:37]([OH:39])=[O:38])C=C.[CH3:40]O.Cl.CN(C)[CH2:45][CH2:46][CH2:47]N=C=NCC>CN(C)C1C=CN=CC=1.C(Cl)Cl>[Cl:36][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=1[C:13]1[CH:12]=[C:11]([CH2:10][N:7]2[CH2:8][CH2:9][NH:4][CH:5]([C:37]([O:39][C:46]([CH3:47])([CH3:40])[CH3:45])=[O:38])[CH2:6]2)[CH:20]=[C:19]2[C:14]=1[CH2:15][NH:16][C:17](=[O:29])[N:18]2[C:21]1[C:22]([Cl:28])=[CH:23][CH:24]=[CH:25][C:26]=1[Cl:27]

Participants

6

Reactant 3

HCID 887MethanolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 226481181-Allyl-4-{[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methyl}piperazine-2-carboxylic acid

Product 1

HCID 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 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-allyl-4-{[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]methyl}piperazine-2-carboxylic acid (EXAMPLE AAA14, 95 mg, 0.16 mmol), methanol (0.02 mL, 0.49 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (47 mg, 0.24 mmol) and 4-(dimethylamino)-pyridine (50 mg, 0.41 mmol) in methylene chloride (1 mL) was stirred at rt for 20 h. Removal of the solvent and subsequent purification by preparative thin layer chromatography using 5% of 2N ammonium in methanol/methylene chloride as eluent provided the title compound as a white solid. 1H NMR (CDCl3, 500 MHz): δ 2.31 (brs, 1H), 2.42 (m, 1H), 2.47 (m, 1H), 2.56 (m, 1H), 2.64 (m, 1H), 3.02 brs, 2H), 3.20 (brs, 1H), 3.32 (m, 1H), 3.42 (m, 2H), 3.65 (s, 3H), 4.25 (dd, 1H, J1=14.2 Hz, J2=6.2 Hz), 4.43 (dd, 1H, J1=14.4 Hz, J2=8.0 Hz), 5.06 (s, 1H), 5.16 (s, 2H), 5.84 (m, 1H), 6.11 (d, 1H, J=13.3 Hz), 6.83 (d, 1H, J=3.2 Hz), 7.30-7.60 (m, 7H). MS (API-ES+): 601 (M+H).

Workup

  1. customRemoval of the solvent and subsequent purification by preparative thin layer chromatography

Sources & evidence

ORD record
ord-fde18fd4a2a2481c80a3360d805eadef
Source dataset
uspto-grants-2004_10
Patent number
US06809199B2

Reaction notes

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