Isopropyl isocyanate → HCID 56677422, compound

HRID 1992089Notes

Reaction equation

HRID 1992089 reaction equation
[CH3:1][C:2]1[N:6]([CH:7]2[CH2:13][CH:12]3[N:14]([CH2:15][CH2:16][C:17]4([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)[CH:9]([CH2:10][CH2:11]3)[CH2:8]2)[C:5]2[CH:29]=[CH:30][CH:31]=[CH:32][C:4]=2[N:3]=1.[CH:33]([N:36]=[C:37]=[O:38])([CH3:35])[CH3:34]>C1COCC1>[CH:33]([NH:36][C:37]([N:20]1[CH2:19][CH2:18][C:17]([CH2:16][CH2:15][N:14]2[CH:12]3[CH2:11][CH2:10][CH:9]2[CH2:8][CH:7]([N:6]2[C:5]4[CH:29]=[CH:30][CH:31]=[CH:32][C:4]=4[N:3]=[C:2]2[CH3:1])[CH2:13]3)([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:22][CH2:21]1)=[O:38])([CH3:35])[CH3:34]

Participants

4

Reactant 2

HCID 61277Isopropyl isocyanateHCID 587278272-Methyl-1-{8-[2-(4-phenyl-4-piperidinyl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole

Product 1

HCID 56677422HCID 56677422, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2-methyl-1-{8-[2-(4-phenylpiperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole (20 mg, 0.047 mmol) in THF (2 mL) was added isopropyl isocyanate (4.3 mg, 0.047 mmol). The resulting mixture was stirred at ambient temperature overnight. After evaporation of the solvent, the residue was purified on silical gel, eluting with a gradient of 10-30% methanol in ethyl acetate to afford N-isopropyl-4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidine-1-carboxamide as white solid (15 mg, 63%). 1H NMR (300 MHz, CDCl3) δ 7.70 (d, J=7.2 Hz, 1H), 7.43-7.38 (m, 2H), 7.34-7.24 (m, 4H), 7.22-7.15 (m, 2H), 4.67 (br, 1H), 4.24 (d, J=7.3 Hz, 1H), 3.99 (m, 1H), 3.62-3.58 (m, 2H), 3.30 (br, 2H), 3.23-3.16 (m, 2H), 2.62 (s, 3H), 2.42 (br, 2H), 2.25-2.20 (m, 2H), 1.98-1.83 (m, 9H), 1.68 (br, 2H), 1.17 (d, J=6.4 Hz, 6H). HRMS m/z (M+H)+ calcd: 514.3546, obsd: 514.3530.

Workup

  1. customAfter evaporation of the solvent
  2. customthe residue was purified on silical gel
  3. washeluting with a gradient of 10-30% methanol in ethyl acetate

Sources & evidence

ORD record
ord-550ccbca847e42649523b97127659572
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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