Trifluoroacetic acid → 4-{N'-[2-(4-fluoro-phenyl)-acetyl]-N'-methyl-hydrazino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1838874Notes

Reaction equation

HRID 1838874 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18](=[O:19])[C:17]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)=[C:16]([C:27]3[CH:32]=[CH:31][N:30]=[C:29]([NH:33][CH:34]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[CH3:35])[N:28]=3)[N:15]2[CH3:42])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=[O:44]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][N:15]([C:16](=[O:44])[CH2:17][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[CH3:42])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:26][C:23]1[CH:22]=[CH:21][C:20]([C:17]2[C:18](=[O:19])[N:14]([CH:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)[N:15]([CH3:42])[C:16]=2[C:27]2[CH:32]=[CH:31][N:30]=[C:29]([NH:33][CH:34]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH3:35])[N:28]=2)=[CH:25][CH:24]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 698631114-{4-(4-Fluorophenyl)-2-methyl-5-oxo-3-[2-(1-phenylethylamino)-pyrimidin-4-yl]-2,5-dihydro-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

Product 2

HCID 102173314-(4-Fluorophenyl)-1-methyl-5-[2-(1-phenylethylamino)-pyrimidin-4-yl]-2-piperidin-4-yl-1,2-dihydropyrazol-3-oneHCID 600611354-{N'-[2-(4-fluoro-phenyl)-acetyl]-N'-methyl-hydrazino}-piperidine-1-carboxylic acid tert-butyl esterYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-{4-(4-fluorophenyl)-2-methyl-5-oxo-3-[2-(1-phenylethylamino)-pyrimidin-4-yl]-2,5-dihydro-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester, 26, (9 g, 15.7 mmol) in CH2Cl2 (90 mL) is added 20% TFA in CH2Cl2. After stirring at room temperature for 0.5 h, the reaction mixture is concentrated in vacuo. Purification by preparatory HPLC affords 4.2 9 (45% yield) of the desired product: [α]D −41.0° (c 1.7, MeOH); 1H NMR (300 MHz, CD3OD) δ 8.25 (d, J=4.8 Hz, 1H), 7.40-7.00 (m, 9H), 6.40 (d, J=4.8 Hz, 1H), 5.11-5.05 (m, 1H), 4.51-4.41 (m, 1H), 3.61-3.55 (m, 2H), 3.33 (bd, J=1.5 Hz, 3H), 3.24-3.05 (m, 3H), 2.92-2.75 (m, 2H), 2.19-2.10 (m, 2H), 1.52 (d, J=6.9 Hz, 3H). HRMS calcd for C27H29FN6O (M+H)+473.2465; found 473.2460.

Workup

  1. concentrationthe reaction mixture is concentrated in vacuo
  2. customPurification by preparatory HPLC

Sources & evidence

ORD record
ord-44365ba50d3044859c5bf9ffc9a4ea81
Source dataset
uspto-grants-2004_01
Patent number
US06677337B2

Reaction notes

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