Triethylamine → HCID 58728400, compound

HRID 1992104Notes

Reaction equation

HRID 1992104 reaction equation
Cl.Cl.[CH3:3][C:4]1[N:8]([CH:9]2[CH2:15][CH:14]3[N:16]([CH2:17][CH2:18][C:19]4([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=5[CH3:31])[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)[CH:11]([CH2:12][CH2:13]3)[CH2:10]2)[C:7]2[CH:32]=[CH:33][CH:34]=[CH:35][C:6]=2[N:5]=1.[C:36]([O:47][CH3:48])(=[O:46])[C:37]1[CH:45]=[CH:44][CH:43]=[C:39]([C:40]([O-])=[O:41])[CH:38]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C)C=O.O>[CH3:3][C:4]1[N:8]([CH:9]2[CH2:15][C@H:14]3[N:16]([CH2:17][CH2:18][C:19]4([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=5[CH3:31])[CH2:20][CH2:21][N:22]([C:40]([C:39]5[CH:38]=[C:37]([CH:45]=[CH:44][CH:43]=5)[C:36]([O:47][CH3:48])=[O:46])=[O:41])[CH2:23][CH2:24]4)[C@H:11]([CH2:12][CH2:13]3)[CH2:10]2)[C:7]2[CH:32]=[CH:33][CH:34]=[CH:35][C:6]=2[N:5]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 69512791,3-Benzenedicarboxylic acid, monomethyl esterHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68676328HCID 68676328, compound

Product 1

HCID 58728400HCID 58728400, compoundYield 47.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-methyl-1-(8-{2-[4-(2-methyl phenyl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-1H-benzimidazole dihydrochloride (0.40 g, 0.84 mmol), monomethyl isophthalate (0.15 g, 0.84 mmol) and triethylamine (0.4 mL, 2.9 mmol) in dimethylformamide (3 mL) was treated with O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (0.35 g, 0.92 mmol) and stirred at rt for 1 h. The mixture was diluted with water and the resultant precipitate was collected, washed with water, dried and purified by chromatography on silica gel eluting with 1:33 methanol:dichloromethane to give methyl 3-{[4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-(2-methylphenyl) piperidin-1-yl]carbonyl}benzoate as a glass (0.240 g, 47%). 1H NMR (400 MHz, CDCl3) δ 8.08 (m, 2H), 7.67 (m, 2H), 7.59 (m, 1H), 7.49 (t, 1H), 7.13-7.29 (m, 6H), 4.62 (m, 1H), 4.11 (m, 1H), 3.93 (s, 3H), 3.56 (m, 2H), 3.26 (m, 2H), 2.54 (m, 5H), 2.36 (m, 4H), 1.95 (m, 10H), 1.64 (m, 4H). HRMS C38H44N4O3 m/z 605.3492 (M+H)Cal. 605.3497 (M+H)Obs..

Workup

  1. customthe resultant precipitate was collected
  2. washwashed with water
  3. customdried
  4. custompurified by chromatography on silica gel eluting with 1:33 methanol

Sources & evidence

ORD record
ord-7101d76c139c45d4a4b854a6d4d88886
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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