1-Propanesulfonyl chloride → N-Methyl-N-[1-(tetrahydro-2H-pyran-4-ylmethyl)-2-(trifluoromethyl)-1H-benzimidazol-5-yl]propane-1-sulfonamide

HRID 1987199Notes

Reaction equation

HRID 1987199 reaction equation
[CH2:1]([S:4](Cl)(=[O:6])=[O:5])[CH2:2][CH3:3].[CH3:8][NH:9][C:10]1[CH:29]=[CH:28][C:13]2[N:14]([CH2:21][CH:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[C:15]([C:17]([F:20])([F:19])[F:18])=[N:16][C:12]=2[CH:11]=1.CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:8][N:9]([C:10]1[CH:29]=[CH:28][C:13]2[N:14]([CH2:21][CH:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[C:15]([C:17]([F:18])([F:19])[F:20])=[N:16][C:12]=2[CH:11]=1)[S:4]([CH2:1][CH2:2][CH3:3])(=[O:6])=[O:5]

Participants

6

Reactant 3

HCID 662791-Propanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 57441079HCID 57441079, compound

Product 1

HCID 57441070N-Methyl-N-[1-(tetrahydro-2H-pyran-4-ylmethyl)-2-(trifluoromethyl)-1H-benzimidazol-5-yl]propane-1-sulfonamideYield 47.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Propane-1-sulfonyl chloride (27 uL, 34 mg, 0.24 mmol) was added to a solution of N-methyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-2-(trifluoromethyl)-1H-benzimidazol-5-amine (63 mg, 0.20 mmol) (see following steps B, C, D, E, F and G for preparation), DIPEA (49 uL, 36 mg, 0.28 mmol) and DMAP (5 mg, 0.04 mmol) in DCM (6 mL) at 0° C. The reaction mixture was stirred overnight at room temperature, diluted with DCM (50 mL), washed with saturated NaHCO3 (2×10 mL) and dried over Na2SO4. The crude product was purified by MPLC using Hex/EtOAc (1:1) on silica gel to give 40 mg (47%) of a white solid as the title compound. 1HNMR (400 MHz, METHANOL-D4): δ 1.00 (t, J=7.42 Hz, 3 H), 1.38-1.53 (m, 4 H), 1.70-1.88 (m, 2 H), 2.15-2.30 (m, 1 H), 3.01-3.11 (m, 2 H), 3.28-3.33 (m, 2 H), 3.35 (s, 3 H), 3.88-3.91 (m, 2 H), 4.30 (d, J=7.62 Hz, 2 H), 7.55 (dd, J=8.79, 1.76 Hz, 1 H), 7.75 (d, J=8.98 Hz, 1 H), 7.82 (d, J=1.56 Hz, 1 H). MS (ESI) (M+H)+=420.0. Anal. Calcd for C18H24F3N3O3S+0.20 H2O+0.30 CH3OH (432.68): C, 50.80; H, 5.96; N, 9.71. Found: C, 50.79; H, 5.91; N, 9.69.

Workup

  1. washwashed with saturated NaHCO3 (2×10 mL)
  2. dry with materialdried over Na2SO4
  3. customThe crude product was purified by MPLC

Sources & evidence

ORD record
ord-6b96deadde3a4203a857a8e89f60d428
Source dataset
uspto-grants-2009_06
Patent number
US07550495B2

Reaction notes

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