Diisopropylethylamine → 1-{[2-(1,1-dimethylpropyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-N-methyl-1H-pyrazole-4-carboxamide

HRID 1435462Notes

Reaction equation

HRID 1435462 reaction equation
Cl.CN.C[CH2:5][N:6](C(C)C)C(C)C.[CH3:13][C:14]([C:18]1[N:22]([CH2:23][CH:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[C:21]2[CH:30]=[CH:31][C:32]([S:34]([N:37]3[CH:41]=[C:40]([C:42]([OH:44])=O)[CH:39]=[N:38]3)(=[O:36])=[O:35])=[CH:33][C:20]=2[N:19]=1)([CH3:17])[CH2:15][CH3:16].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:17][C:14]([C:18]1[N:22]([CH2:23][CH:24]2[CH2:25][CH2:26][O:27][CH2:28][CH2:29]2)[C:21]2[CH:30]=[CH:31][C:32]([S:34]([N:37]3[CH:41]=[C:40]([C:42]([NH:6][CH3:5])=[O:44])[CH:39]=[N:38]3)(=[O:35])=[O:36])=[CH:33][C:20]=2[N:19]=1)([CH3:13])[CH2:15][CH3:16]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 6364545Methylamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579373031-(2-tert-pentyl-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-benzo[d]imidazol-5-ylsulfonyl)-1H-pyrazole-4-carboxylic acid

Product 1

HCID 236604861-{[2-(1,1-dimethylpropyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-N-methyl-1H-pyrazole-4-carboxamideYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Following the same procedure in Example 24, Step A, using methylamine hydrochloride (24 mg, 0.36 mmol), DIPEA (104 uL, 77 mg, 0.59 mmol), 1-{[2-(1,1-dimethylpropyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-1H-pyrazole-4-carboxylic acid (0.18 mmol) (see following Steps B and C for preparation) and HATU (109 mg, 0.29 mmol) in DMF (3 mL). The crude product was purified by MPLC using Hex/EtOAc (1:9) on silica gel to give 78 mg (92%) of a white solid as the title compound. 1H NMR (400 MHz, METHANOL-D4) δ 0.78 (t, J=7.52 Hz, 3 H), 1.40-1.57 (m, 4 H), 1.59 (s, 6 H), 1.95 (q, J=7.29 Hz, 2 H), 2.21-2.37 (m, 1 H), 2.82 (s, 3 H), 3.25-3.35 (m, 2 H), 3.85-3.94 (m, 2 H), 4.42 (d, J=7.42 Hz, 2 H), 7.94 (d, J=9.0 Hz, 1 H), 8.00 (dd, J=8.8, 1.7 Hz, 1 H), 8.02 (d, J=0.59 Hz, 1 H), 8.35 (d, J=1.56 Hz, 1 H), 8.72 (d, J=0.59 Hz, 1 H); MS (ESI) (M+H)+=474.0; Anal. Calcd for C23H31N5O4S+1.10 TFA+0.4H2O (606.23): C, 49.93; H, 5.47; N, 11.55. Found: C, 49.95; H, 5.44; N, 11.48.

Workup

  1. customThe crude product was purified by MPLC

Sources & evidence

ORD record
ord-40aafc1366fa4b198e546c8c8366d4c9
Source dataset
uspto-grants-2009_11
Patent number
US07615642B2

Reaction notes

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