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

Participants

Role	Name	HCID	Charge
Reactant	Cyclopropylamine	HCID 69828	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	1-(2-tert-pentyl-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-benzo[d]imidazol-5-ylsulfonyl)-1H-pyrazole-4-carboxylic acid	HCID 57937303	—
Solvent	Dimethylformamide	HCID 6228	—
Product	N-Cyclopropyl-1-{[2-(1,1-dimethylpropyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-1H-pyrazole-4-carboxamide	HCID 23660488	42.3%

Reaction Steps

Following the same procedure in Example 24, Step A, using cyclopropylamine (21 mg, 25 uL, 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) and HATU (109 mg, 0.29 mmol) in DMF (3 mL). The crude product was purified by MPLC using Hex/EtOAc (1:4) on silica gel to give 38 mg (42%) of a white solid as the title compound. 1H NMR (400 MHz, METHANOL-D4) δ 0.54-0.61 (m, 2 H), 0.74-0.82 (m, 5 H), 1.42-1.58 (m, 4 H), 1.60 (s, 6 H), 1.96 (q, J=7.55 Hz, 2 H), 2.22-2.36 (m, 1 H), 2.73-2.80 (m, 1 H), 3.26-3.36 (m, 2 H), 3.86-3.95 (m, 2 H), 4.42 (d, J=7.42 Hz, 2 H), 7.92 (d, J=8.8 Hz, 1 H), 7.98 (dd, J=8.8, 1.8 Hz, 1 H), 8.05 (s, 1 H), 8.34 (d, J=1.76 Hz, 1 H), 8.76 (s, 1 H); MS (ESI) (M+H)+=500.0; Anal. Calcd for C25H33N5O4S+0.6 TFA+1.0H2O (586.07): C, 53.70; H, 6.12; N, 11.95. Found: C, 53.65; H, 5.98; N, 12.02.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07615642B2
Source dataset	uspto-grants-2009_11
ORD ID	ord-94a7b7eea6284ed4bcc9231f6c1dee25
Source note	uspto-grants-2009_11