Trimethylsilyl isocyanate → 1-[3-Chloro-2-(4-{3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperazin-1-yl)-phenyl]-3-methyl-urea

HRID 132916Notes

Reaction equation

HRID 132916 reaction equation
[Cl:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][N:18]3[C:26]4[CH2:25][CH2:24][N:23]([S:27]([CH3:30])(=[O:29])=[O:28])[CH2:22][C:21]=4[C:20]([C:31]4[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][CH:32]=4)=[N:19]3)[CH2:11][CH2:10]2)=[C:4]([NH2:8])[CH:5]=[CH:6][CH:7]=1.C[Si]([N:45]=[C:46]=[O:47])(C)C.CO.[CH2:50](Cl)Cl>C(Cl)Cl>[Cl:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][N:18]3[C:26]4[CH2:25][CH2:24][N:23]([S:27]([CH3:30])(=[O:28])=[O:29])[CH2:22][C:21]=4[C:20]([C:31]4[CH:32]=[CH:33][C:34]([C:37]([F:38])([F:39])[F:40])=[CH:35][CH:36]=4)=[N:19]3)[CH2:11][CH2:10]2)=[C:4]([NH:8][C:46]([NH:45][CH3:50])=[O:47])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 70696Trimethylsilyl isocyanate2×HCID 102107373-Chloro-2-(4-{3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperazin-1-yl)-phenylamineHCID 21226129Dichloromethane methanol

Product 1

HCID 101684941-[3-Chloro-2-(4-{3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperazin-1-yl)-phenyl]-3-methyl-ureaYield 22%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 3-chloro-2-(4-{3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperazin-1-yl)-phenylamine (0.062 g, 0.104 mmol) in CH2Cl2 (0.52 mL) was added trimethylsilyl isocyanate (0.017 mL, 0.125 mmol). The reaction mixture was allowed to stir for 48 h at room temperature. The reaction had not gone to completion, so an additional 0.017 mL (0.125 mmol) of trimethylsilyl isocyanate was added and the reaction was heated to 45° C. for 10 h. Column chromatography (silica, 3-10% MeOH/CH2Cl2) afforded 1-[3-chloro-2-(4-{3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperazin-1-yl)-phenyl]-3-methyl-urea (0.015 g, 22%). MS (electrospray): exact mass calculated for C28H33ClF3N7O3S, 639.2; m/z found, 640.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.26 (br s, 1H), 8.05 (d, J=8.2 Hz, 1H), 7.73 (d, J=8.2 Hz, 2H), 7.66 (d, J=8.2 Hz, 2H), 7.09 (t, J=8.2 Hz, 1H), 6.92 (d, J=8.2 Hz, 1H), 4.65 (s, 2H), 4.55 (s, 2H), 4.15 (t, J=6.7 Hz, 2H), 3.65-3.73 (m, 4H), 2.96 (t, J=5.6 Hz, 2H), 2.87-2.92 (m, 2H), 2.91 (s, 3H), 2.70 (d, J=11.4 Hz, 2H), 2.40 (t, J=6.7 Hz, 2H), 2.09-2.22 (m, 4H).

Workup

  1. temperaturethe reaction was heated to 45° C. for 10 h

Sources & evidence

ORD record
ord-06249ae0f6644394b904d156d4210445
Source dataset
uspto-grants-2008_06
Patent number
US07388011B2

Reaction notes

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