Water → HCID 178522437, compound

HRID 2274437Notes

Reaction equation

HRID 2274437 reaction equation
O.C(OC([N:9]1[CH2:14][CH2:13][N:12]([C:15]2[C:43]([F:44])=[CH:42][C:18]3[N:19]=[C:20]([C:22]4[C:26]([NH:27][C:28]([N:30]5[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]5)=[O:29])=[CH:25][N:24](C5CCCCO5)[N:23]=4)[NH:21][C:17]=3[CH:16]=2)[CH2:11][CH2:10]1)=O)(C)(C)C>FC(F)(F)C(O)=O>[F:44][C:43]1[C:15]([N:12]2[CH2:13][CH2:14][NH:9][CH2:10][CH2:11]2)=[CH:16][C:17]2[NH:21][C:20]([C:22]3[C:26]([NH:27][C:28]([N:30]4[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]4)=[O:29])=[CH:25][NH:24][N:23]=3)=[N:19][C:18]=2[CH:42]=1

Participants

4

Reactant 2

HCID 962WaterHCID 178452210HCID 178452210, compound

Product 1

HCID 178522437HCID 178522437, compoundYield 74.2%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
22 °C

Procedure

0.5 mL of water is added to a solution of 380 mg of 4-{6-fluoro-2-[4-[(piperidine-1-carbonyl)amino]-1-(tetrahydropyran-2-yl)-1H-pyrazol-3-yl]-3H-benzimidazol-5-yl}piperazine-1-carboxylic acid tert-butyl ester in solution in 2 mL of trifluoroacetic acid. The reaction medium is stirred at 22° C. for 48 hours. The reaction medium is concentrated under vacuum in a rotary evaporator. The reaction crude is purified by flash chromatography on an Intelliflash apparatus on an Analogix RS-40 cartridge. The elution is carried out with pure dichloromethane and then with dichloromethane containing 5% of ammoniacal methanol. 195 mg of N-[3-(5-fluoro-6-piperazin-1-yl-1H-benzimidazol-2-yl)-1H-pyrazol-4-yl]-piperidine-1-carboxamide are obtained in the form of a yellow solid. 1H NMR (400 MHz, DMSO-d6, δ in ppm): from 1.48 to 1.68 (m, 6H); 3.23 (m, 4H); 3.30 (m, 4H); 3.47 (m, 4H); 7.24 (d, J=8.0 Hz, 1H); 7.48 (d, J=11.5 Hz, 1H); 8.01 (s, 1H). ES mass spectrum: m/z=413 MH+, m/z=328 (M+H—C5H11N)+, m/z=227.9 (M+CH3CN+2H)2+/2 (base peak). Remark: the acetonitrile explaining the m/z=227.9 peak is in the mobile phase.

Workup

  1. concentrationThe reaction medium is concentrated under vacuum in a rotary evaporator
  2. customThe reaction crude
  3. customis purified by flash chromatography on an Intelliflash apparatus on an Analogix RS-40 cartridge
  4. washThe elution

Sources & evidence

ORD record
ord-e09c41c0351648e0a052b26b5f9566ea
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

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