Diisopropylethylamine → 1-{[2-tert-Butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-N-(cyclobutylmethyl)-1H-pyrazole-4-carboxamide

HRID 1435481Notes

Reaction equation

HRID 1435481 reaction equation
[CH:1]1([CH2:5][NH2:6])[CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:40]([C:44]1[N:48]([CH2:49][CH:50]2[CH2:55][CH2:54][O:53][CH2:52][CH2:51]2)[C:47]2[CH:56]=[CH:57][C:58]([S:60]([N:63]3[CH:67]=[C:66]([C:68](O)=[O:69])[CH:65]=[N:64]3)(=[O:62])=[O:61])=[CH:59][C:46]=2[N:45]=1)([CH3:43])([CH3:42])[CH3:41]>CN(C=O)C>[C:40]([C:44]1[N:48]([CH2:49][CH:50]2[CH2:55][CH2:54][O:53][CH2:52][CH2:51]2)[C:47]2[CH:56]=[CH:57][C:58]([S:60]([N:63]3[CH:67]=[C:66]([C:68]([NH:6][CH2:5][CH:1]4[CH2:4][CH2:3][CH2:2]4)=[O:69])[CH:65]=[N:64]3)(=[O:62])=[O:61])=[CH:59][C:46]=2[N:45]=1)([CH3:43])([CH3:41])[CH3:42]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 409746CyclobutylmethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579372951-{[2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-1H-pyrazole-4-carboxylic acid

Product 1

HCID 236609991-{[2-tert-Butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-N-(cyclobutylmethyl)-1H-pyrazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Following the same procedure in example 53, step A, using (cyclobutylmethyl)amine (12 mg, 0.13 mmol), HATU (37 mg, 0.09 mmol), DIPEA (0.02 mL, 0.10 mmol) and 1-{[2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-1H-pyrazole-4-carboxylic acid (40 mg, 0.09 mmol) in DMF (5 mL). The crude product was purified by MPLC on silica gel using EtOAc/DCM (1:1) to provide the title compound as a white solid. The product was converted to its TFA salt. Yield: 27 mg (48%); 1H NMR (400 MHz, CD3OD) δ 1.43-1.51 (m, 3 H), 1.55 (dd, J=12.30, 3.91 Hz, 1 H), 1.61 (s, 9 H), 1.66-1.78 (m, 2 H), 1.81-1.93 (m, 2 H), 1.99-2.10 (m, 2 H), 2.26-2.37 (m, 1 H), 2.48-2.59 (m, 1 H), 3.26-3.36 (m, 4 H), 3.90 (dd, J=11.13, 3.71 Hz, 2 H), 4.45 (d, J=7.42 Hz, 2 H), 7.94-8.04 (m, 2 H), 8.05 (d, J=0.78 Hz, 1 H), 8.36 (d, J=1.37 Hz, 1 H), 8.76 (s, 1 H); MS (ESI) (M+H)+=513.7; Anal. Calcd for C26H35N5O4S+1.8 TFA+2.4H2O: C, 46.65; H, 5.50; N, 9.19. Found: C, 46.74; H, 5.61; N, 8.97.

Workup

  1. customThe crude product was purified by MPLC on silica gel

Sources & evidence

ORD record
ord-5152494aeafd4be7ab0ae87e64f5aa72
Source dataset
uspto-grants-2009_11
Patent number
US07615642B2

Reaction notes

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