Cyclobutylamine → 1-{[2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-N-cyclobutyl-1H-pyrrole-3-carboxamide

HRID 1435449Notes

Reaction equation

HRID 1435449 reaction equation
CCN(C(C)C)C(C)C.[C:10]([C:14]1[N:18]([CH2:19][CH:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[C:17]2[CH:26]=[CH:27][C:28]([S:30]([N:33]3[CH:37]=[CH:36][C:35]([C:38]([OH:40])=O)=[CH:34]3)(=[O:32])=[O:31])=[CH:29][C:16]=2[N:15]=1)([CH3:13])([CH3:12])[CH3:11].[CH:41]1([NH2:45])[CH2:44][CH2:43][CH2:42]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[C:10]([C:14]1[N:18]([CH2:19][CH:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[C:17]2[CH:26]=[CH:27][C:28]([S:30]([N:33]3[CH:37]=[CH:36][C:35]([C:38]([NH:45][CH:41]4[CH2:44][CH2:43][CH2:42]4)=[O:40])=[CH:34]3)(=[O:32])=[O:31])=[CH:29][C:16]=2[N:15]=1)([CH3:12])([CH3:13])[CH3:11]

Participants

7

Reactant 4

HCID 75645CyclobutylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579373191-{[2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-1H-pyrrole-3-carboxylic acid

Product 1

HCID 236603061-{[2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-N-cyclobutyl-1H-pyrrole-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (0.1 mL, 74 mg, 0.57 mmol) was added to a solution of 1-{[2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-1H-pyrrole-3-carboxylic acid (0.078 mmol) (see following step B for preparation) and cyclobutylamine (0.1 mL, 83 mg, 1.17 mmol) in DMF (5 mL) at 0° C. Stirring for 20 min, HATU (100 mg, 0.31 mmol) was added at 0° C. The reaction mixture was stirred overnight at room temperature, diluted with H2O (50 mL) and extracted with EtOAc (3×25 mL). The combined organic phases were washed with H2O (2×10 mL), NaCl (10 mL) and dried over Na2SO4. The crude product was purified by MPLC using Hex/EtOAc (3:7) on silica gel to 30 mg (78%) of a white solid as the title compound. 1H NMR (400 MHz, METHANOL-D4) δ 1.41-1.57 (m, 4 H), 1.60 (s, 9 H), 1.66-1.78 (m, 2 H), 1.95-2.09 (m, 2 H), 2.20-2.35 (m, 3 H), 3.25-3.34 (m, 2 H), 3.85-3.93 (m, 2 H), 4.33-4.41 (m, 1 H), 4.43 (d, J=7.62 Hz, 2 H), 6.67 (dd, J=3.32, 1.56 Hz, 1 H), 7.28 (dd, J=3.32, 2.34 Hz, 1 H), 7.81-7.84 (m, 1 H), 7.91-7.95 (m, 1 H), 7.95-7.99 (m, 1 H), 8.26 (dd, J=1.66, 0.68 Hz, 1 H); MS (ESI) (M+H)+=498.8; Anal. Calcd for C26H34N4O4S+0.90 TFA+0.80H2O (615.68): C, 54.23; H, 5.98; N, 9.10. Found: C, 54.25; H, 6.02; N, 9.12.

Workup

  1. stirringThe reaction mixture was stirred overnight at room temperature
  2. extractionextracted with EtOAc (3×25 mL)
  3. washThe combined organic phases were washed with H2O (2×10 mL), NaCl (10 mL)
  4. dry with materialdried over Na2SO4
  5. customThe crude product was purified by MPLC

Sources & evidence

ORD record
ord-4869791b6b9346aaad90ada6d13b912f
Source dataset
uspto-grants-2009_11
Patent number
US07615642B2

Reaction notes

Loading…