Acetyl chloride → HCID 66729602, compound

HRID 516641Notes

Reaction equation

HRID 516641 reaction equation
[C:1]([NH:5][C:6]1[CH:11]=[C:10]([C:12]2[C:13]([C:23]3[C:24]([F:44])=[C:25]([N:29]([CH2:41][O:42][CH3:43])[S:30]([C:33]4[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=4[F:40])(=[O:32])=[O:31])[CH:26]=[CH:27][CH:28]=3)=[N:14][N:15]([CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)[CH:16]=2)[CH:9]=[CH:8][N:7]=1)([CH3:4])([CH3:3])[CH3:2].[C:45](Cl)(=[O:47])[CH3:46]>C(Cl)Cl>[C:45]([N:20]1[CH2:19][CH2:18][CH:17]([N:15]2[CH:16]=[C:12]([C:10]3[CH:9]=[CH:8][N:7]=[C:6]([NH:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH:11]=3)[C:13]([C:23]3[C:24]([F:44])=[C:25]([N:29]([CH2:41][O:42][CH3:43])[S:30]([C:33]4[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=4[F:40])(=[O:32])=[O:31])[CH:26]=[CH:27][CH:28]=3)=[N:14]2)[CH2:22][CH2:21]1)(=[O:47])[CH3:46]

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 86693837HCID 86693837, compound

Product 1

HCID 66729602HCID 66729602, compoundYield 87.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of N-{3-[4-(2-tert-Butylamino-pyridin-4-yl)-1-piperidin-4-yl-1H-pyrazol-3-yl]-2-fluoro-phenyl}-2,5-difluoro-N-methoxymethyl-benzenesulfonamide (100 mg, 0.159 mmol) (prepared as described in example 8) in DCM (1.5 mL) triethylamine (0.024 mL, 0.175 mmol, 1.1 eq) was added, followed by acetylchloride (0.011 mL, 0.159 mmol, 1 eq) and the solution was stirred at r.t. for 1 h. The reaction mixture was then diluted with DCM and washed with water. The aqueous phase was back extracted with DCM. The combined organic layers were washed with brine, dried over Na2SO4 and evaporated to dryness. The crude product was purified by flash chromatography (DCM/MeOH/NH3 7N in MeOH 94.5:1) affording 93 mg (87%) of N-{3-[1-(1-Acetyl-piperidin-4-yl)-4-(2-tert-butylamino-pyridin-4-yl)-1H-pyrazol-3-yl]-2-fluoro-phenyl}-2,5-difluoro-N-methoxymethyl-benzenesulfonamide, HPLC (254 nm): Rt: 6.59 min; 1H NMR (DMSO-d6) Shift: 8.18 (s, 1H), 7.77 (d, J=5.2 Hz, 1H), 7.58-7.66 (m, 1H), 7.45-7.58 (m, 3H), 7.23-7.35 (m, 2H), 6.26 (s, 1H), 6.15 (dd, J=1.1, 5.4 Hz, 1H), 5.76 (br. s., 1H), 5.01 (s, 2H), 4.43-4.56 (m, 2H), 3.89-3.97 (m, 1H), 3.30 (s, 3H), 3.17-3.25 (m, 1H), 2.69-2.78 (m, 1H), 2.02-2.16 (m, 2H), 2.05 (s, 3H), 1.94 (qd, J=4.6, 12.1 Hz, 1H), 1.79 (qd, J=4.5, 12.1 Hz, 1H), 1.31 (s, 9H); HRMS (ESI) calcd for C33H38F3N6O4S [M+H]+ 671.2622. found 671.2623.

Workup

  1. washwashed with water
  2. extractionThe aqueous phase was back extracted with DCM
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. customevaporated to dryness
  6. customThe crude product was purified by flash chromatography (DCM/MeOH/NH3 7N in MeOH 94.5:1)

Sources & evidence

ORD record
ord-ba1e2cc1b2dc4e0c9b38dddf52e27e27
Source dataset
uspto-grants-2015_08
Patent number
US09114137B2

Reaction notes

Loading…