Diisopropylethylamine → 2-Chloro-3,6-difluoro-n-{1-methyl-1-[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]ethyl}benzamide

HRID 1169833Notes

Reaction equation

HRID 1169833 reaction equation
[CH3:1][C:2]([NH2:22])([C:4]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[CH2:9][CH2:8][N:7]([S:10]([CH2:13][CH2:14][CH3:15])(=[O:12])=[O:11])[CH2:6][CH2:5]1)[CH3:3].CCN(C(C)C)C(C)C.[Cl:32][C:33]1[C:41]([F:42])=[CH:40][CH:39]=[C:38]([F:43])[C:34]=1[C:35](Cl)=[O:36]>CN(C=O)C>[Cl:32][C:33]1[C:41]([F:42])=[CH:40][CH:39]=[C:38]([F:43])[C:34]=1[C:35]([NH:22][C:2]([CH3:3])([C:4]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[CH2:9][CH2:8][N:7]([S:10]([CH2:13][CH2:14][CH3:15])(=[O:12])=[O:11])[CH2:6][CH2:5]1)[CH3:1])=[O:36]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27735362-Chloro-3,6-difluorobenzoyl chlorideHCID 59003529{1-Methyl-1-[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]ethyl}amine

Product 1

HCID 116989752-Chloro-3,6-difluoro-n-{1-methyl-1-[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]ethyl}benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of {1-Methyl-1-[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]ethyl}amine (II-1, 43 mg, 0.13 mmol) in DMF (0.7 mL) was treated with i-Pr2NEt (0.066 mL, 0.38 mmol) and 2-chloro-3,6,-difluorobenzoyl chloride (0.2 mL, 0.8 mmol) and stirred at room temperature for 1.5 h. The reaction mixture was purified directly by reverse phase HPLC to afford 2-chloro-3,6-difluoro-N-{1-methyl-1-[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]ethyl}benzamide (II-2). Analytical LCMS: single peak (214 nm), 2.803 min. 1H NMR (CD3OD, 300 M ) δ 8.67 (d, J=3.9 Hz, 1H), 8.51 (s, 1H), 8.15 (ddd, J=1.8, 7.8, 8.1 Hz, 1H), 7.88 (d, J=8.4 Hz, 1H), 7.60 (dd, J=5.5, 6.9 Hz, 1H), 7.34 (ddd, J=4.8, 9.3, 14.1 Hz, 1H), 7.21 (ddd, J=4.2, 8.4, 12.3 Hz), 1H), 3.76-3.65 (m, 2H), 2.86-2.78 (m, 4H), 2.69-2.54 (m, 2H), 2.25-2.15 (m, 2H), 1.76-1.63 (m, 2H), 1.43 (s, 6H), 0.98 (t, J=7.2 Hz, 3H); RMS m/z 500.1572 (C22H28ClF2N3O3S+H+ requires 500.1581).

Workup

  1. customThe reaction mixture was purified directly by reverse phase HPLC

Sources & evidence

ORD record
ord-93635aaf03a04cc4b4b7d8fc21b5bcac
Source dataset
uspto-grants-2010_11
Patent number
US07825135B2

Reaction notes

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