Diisopropylethylamine → HCID 57937293, compound

HRID 1435516Notes

Reaction equation

HRID 1435516 reaction equation
Cl.[OH:2][CH:3]1[CH2:6][NH:5][CH2:4]1.C(N(CC)C(C)C)(C)C.[C:16]([C:20]1[N:24]([CH2:25][CH:26]2[CH2:31][CH2:30][C:29]([F:33])([F:32])[CH2:28][CH2:27]2)[C:23]2[CH:34]=[CH:35][C:36]([S:38](Cl)(=[O:40])=[O:39])=[CH:37][C:22]=2[N:21]=1)([CH3:19])([CH3:18])[CH3:17]>ClCCl.CCOC(C)=O>[C:16]([C:20]1[N:24]([CH2:25][CH:26]2[CH2:27][CH2:28][C:29]([F:33])([F:32])[CH2:30][CH2:31]2)[C:23]2[CH:34]=[CH:35][C:36]([S:38]([N:5]3[CH2:6][CH:3]([OH:2])[CH2:4]3)(=[O:39])=[O:40])=[CH:37][C:22]=2[N:21]=1)([CH3:19])([CH3:17])[CH3:18]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 27592903-Hydroxyazetidine hydrochlorideHCID 579372942-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazole-5-sulfonyl chloride

Product 1

HCID 57937293HCID 57937293, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

3-Hydroxyazetidine hydrochloride (162 mg, 1.5 mmol) was dissolved in 7 mL of dry dichloromethane. N,N-diisopropylethylamine (0.7 mL, 4 mmol) was added and the mixture was cooled down to 0° C. 2-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazole-5-sulfonyl chloride (400 mg, 1 mmol) was slowly added to the reaction mixture which was allowed to warm to room temperature for 2 hours. The mixture was diluted with EtOAc which washed with water then brine and dried over Na2SO4. The solvent was removed in vacuo to give a crude product that was purified by LCMS using high pH column 40-70% acetonitrile gradient to give 340 mg (62%) of a white solid as the title compound. 1H NMR (400 MHz, METHANOL-D4) δ 1.56-1.66 (m, 2 H), 1.69 (s, 9 H), 1.73-1.84 (m, 4 H), 2.01-2.14 (m, 3 H), 3.45-3.51 (m, 2 H), 4.01 (dd, J=8.79, 6.84 Hz, 2 H), 4.34-4.43 (m, 1 H), 4.58 (d, J=7.62 Hz, 2 H), 7.97 (dd, J=8.79, 1.56 Hz, 1 H), 8.13 (d, J=8.79 Hz, 1 H), 8.18 (d, J=1.76 Hz, 1 H); MS (APPI) (M+H)+=442.3; Anal. Calc. for C21H29F2N3O3S+4.9C2HO2F3+5.0H2O+2.7 CH3CN: C, 39.47; H, 4.14; N, 6.31. Found: C, 39.48; H, 4.14; N, 6.30

Workup

  1. temperatureto warm to room temperature for 2 hours
  2. washwashed with water
  3. dry with materialbrine and dried over Na2SO4
  4. customThe solvent was removed in vacuo
  5. customto give a crude product that
  6. customwas purified by LCMS

Sources & evidence

ORD record
ord-ddc7ff48961049e09df0daa6e8d013e3
Source dataset
uspto-grants-2009_11
Patent number
US07615642B2

Reaction notes

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