Triethylamine → HCID 58728137, compound

HRID 1992228Notes

Reaction equation

HRID 1992228 reaction equation
Cl.Cl.[O:3]1[C:7]2[CH:8]=[CH:9][C:10]([C:12]3([CH2:18][CH2:19][N:20]4[CH:25]5[CH2:26][CH2:27][CH:21]4[CH2:22][CH:23]([N:28]4[C:32]6[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=6[N:30]=[C:29]4[CH3:37])[CH2:24]5)[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)=[CH:11][C:6]=2[O:5][CH2:4]1.C(N(CC)CC)C.[CH3:45][C:46]([CH3:52])([CH2:50][OH:51])[C:47](O)=[O:48].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.ClCCl>[O:3]1[C:7]2[CH:8]=[CH:9][C:10]([C:12]3([CH2:18][CH2:19][N:20]4[C@H:25]5[CH2:26][CH2:27][C@@H:21]4[CH2:22][CH:23]([N:28]4[C:32]6[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=6[N:30]=[C:29]4[CH3:37])[CH2:24]5)[CH2:13][CH2:14][N:15]([C:47](=[O:48])[C:46]([CH3:52])([CH3:45])[CH2:50][OH:51])[CH2:16][CH2:17]3)=[CH:11][C:6]=2[O:5][CH2:4]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 785483-Hydroxy-2,2-dimethylpropionic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68677071HCID 68677071, compound

Product 1

HCID 58728137HCID 58728137, compoundYield 59%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-(8-{2-[4-(1,3-benzodioxol-5-yl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole dihydrochloride (0.20 g, 0.39 mmol), triethylamine (0.17 mL, 1.25 mmol) and 2,2-dimethyl-3-hydroxypropionic acid (46 mg, 0.39 mmol) in dimethylformamide (1.25 mL) was treated with O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (163 mg, 0.43 mmol) and the resulting mixture was stirred for 1 h at rt. The mixture was diluted with water and the resulting gummy precipitate was dissolved in dichloromethane, washed with saturated sodium bicarbonate solution, with water, dried and purified by chromatography on silica gel eluting with a dichloromethane to methanol-dichloromethane 1:9 gradient to give 3-(4-(1,3-benzodioxol-5-yl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-1-yl)-2,2-dimethyl-3-oxopropan-1-ol as a solid (0.13 g, 59%). 1H NMR (400 MHz, CDCl3) δ 7.66 (m, 1H), 7.29 (m, 1H), 7.15 (m, 2H), 6.80 (m, 2H), 6.73 (m, 1H), 5.97 (s, 2H), 4.62 (m, 1H), 3.92 (m, 2H), 3.75 (m, 1H), 3.46 (s, 2H), 3.26 (m, 4H), 2.57 (s, 3H), 2.38 (m, 2H), 2.14 (m, 2H), 1.91-2.00 (m, 6H), 1.70-1.78 (m, 4H), 1.64 (m, 2H), 1.25 (s, 6H). HRMS C34H44N4O4 m/z 573.3441 (M+H)Cal. 573.3428 (M+H)Obs..

Workup

  1. washwashed with saturated sodium bicarbonate solution, with water
  2. customdried
  3. custompurified by chromatography on silica gel eluting with a dichloromethane to methanol-dichloromethane 1:9 gradient

Sources & evidence

ORD record
ord-7a5c53e8485042d899baec898afd3a59
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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