Diisopropylethylamine → 3,4-Dihydro-3-(1-(2-(3-methyl-4-oxo-2-phenylthiazolidin-5-yl)acetyl)piperidin-4-yl)quinazolin-2(1H)-one

HRID 1695899Notes

Reaction equation

HRID 1695899 reaction equation
[CH3:1][N:2]1[C:6](=[O:7])[CH:5]([CH2:8][C:9]([OH:11])=O)[S:4][CH:3]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.OC(C(F)(F)F)=O.[NH:25]1[CH2:30][CH2:29][CH:28]([N:31]2[CH2:40][C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[NH:33][C:32]2=[O:41])[CH2:27][CH2:26]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CC#N>[CH3:1][N:2]1[C:6](=[O:7])[CH:5]([CH2:8][C:9]([N:25]2[CH2:26][CH2:27][CH:28]([N:31]3[CH2:40][C:39]4[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=4)[NH:33][C:32]3=[O:41])[CH2:29][CH2:30]2)=[O:11])[S:4][CH:3]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595549922-(3-Methyl-4-oxo-2-phenylthiazolidin-5-yl)acetic acidHCID 691875533,4-dihydro-3-(piperidin-4-yl)quinazolin-2(1H)-one TFA

Product 1

HCID 595551023,4-Dihydro-3-(1-(2-(3-methyl-4-oxo-2-phenylthiazolidin-5-yl)acetyl)piperidin-4-yl)quinazolin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-(3-methyl-4-oxo-2-phenylthiazolidin-5-yl)acetic acid (0.2 mmol, 50 mg), 3,4-dihydro-3-(piperidin-4-yl)quinazolin-2(1H)-one TFA salt (0.15 mmol, 49 mg) and DIPEA (0.375 mmol, 65.3 μl) in 4:1 CH3CN:DMF (0.5 ml) was added HATU (0.18 mmol, 68 mg) and the reaction mixture was stirred at room temperature for 16 h. Purification by preparative reverse phase HPLC using 10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA) gave the title compound. LC/MS (10% to 99%): M/Z (M+H)+ (obs)=465.5; tR=2.18. 1H NMR (400 MHz, CDCl3) δ 7.34-7.22 (m, 5H), 7.12 (t, J=7.5 Hz, 1H), 7.00 (d, J=7.5 Hz, 2H), 6.95-6.89 (m, 2H), 6.61 (d, J=7.8 Hz, 2H), 5.46-5.41 (m, 1H), 4.70 (m, 1H), 4.56 (m, 1H), 4.26 (m, 3H), 3.86 (m, 1H), 3.50 (m, 1H), 3.32 (m, 1H), 3.12-3.08 (m, 1H), 2.89-2.73 (m, 1H), 1.69 (m, 3H) ppm.

Workup

  1. customPurification by preparative reverse phase

Sources & evidence

ORD record
ord-026d0b912f9a4d3d928822a76e64854c
Source dataset
uspto-grants-2012_04
Patent number
US08163737B2

Reaction notes

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