Diisopropylethylamine → 1-((1R,5S)-8-{2-[3-(2,2-dimethylpropanoyl)-6-phenyl-1,3-oxazinan-6-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole

HRID 271995Notes

Reaction equation

HRID 271995 reaction equation
[CH3:1][C:2]([CH3:21])([CH3:20])[C:3]([N:5]1[CH2:10][CH2:9][C:8]([CH2:17][CH:18]=O)([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[O:7][CH2:6]1)=[O:4].Cl.Cl.[C@@H:24]12[NH:31][C@@H:28]([CH2:29][CH2:30]1)[CH2:27][CH:26]([N:32]1[C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=3[N:34]=[C:33]1[CH3:41])[CH2:25]2.C(N(C(C)C)CC)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH3:21][C:2]([CH3:1])([CH3:20])[C:3]([N:5]1[CH2:10][CH2:9][C:8]([CH2:17][CH2:18][N:31]2[C@H:28]3[CH2:29][CH2:30][C@@H:24]2[CH2:25][CH:26]([N:32]2[C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=4[N:34]=[C:33]2[CH3:41])[CH2:27]3)([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[O:7][CH2:6]1)=[O:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 59835994HCID 59835994, compoundHCID 689368471-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl]-2-methyl-1H-benzimidazole dihydrochloride

Product 1

HCID 103241881-((1R,5S)-8-{2-[3-(2,2-dimethylpropanoyl)-6-phenyl-1,3-oxazinan-6-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazoleYield 57.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of [3-(2,2-dimethylpropanoyl)-6-phenyl-1,3-oxazinan-6-yl]acetaldehyde (50.4 mg, 0.17 mmol), 1-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl]-2-methyl-1H-benzimidazole dihydrochloride (64 mg, 0.17 mmol) and diisopropylethylamine (0.063 mL, 0.35 mmol) in 2 mL CH2Cl2 was added sodium triacetoxyborohydride (55 mg, 0.26 mmol) and the reaction mixture was stirred for 2 h at room temperature. After evaporation, the residue was chromatographed (5% (2M NH3/MeOH) in CHCl3) to provide 1-((1R,5S)-8-{2-[3-(2,2-dimethylpropanoyl)-6-phenyl-1,3-oxazinan-6-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole (50.4 mg, 56%) as a white solid. 1H NMR (400 MHz, CDCl3): δ 7.65 (m, 1H), 7.43-7.34 (m, 4H), 7.32-7.26 (m, 2H), 7.19-7.11 (m, 2H), 5.43 (s, 1H, J=11.2 Hz), 4.70 (d, 1H, J=10.3 Hz), 4.61 (m, 1H), 4.21 (m, 1H), 3.42-3.22 (m, 2H), 3.08 (m, 1H), 2.57 (s, 3H), 2.43-1.57 (m, 14H), 1.28 (s, 9H); ESI-MS 515 (M+H), 237 (M+Na).

Workup

  1. customAfter evaporation
  2. customthe residue was chromatographed (5% (2M NH3/MeOH) in CHCl3)

Sources & evidence

ORD record
ord-67443ab34f634fba913457ac177756ca
Source dataset
uspto-grants-2008_11
Patent number
US07452992B2

Reaction notes

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