Diisopropylethylamine → 1-{8-[2-(4-(3-fluorophenyl)-1-{[3-(trifluoromethyl)pyridin-2-yl]carbonyl}piperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-2-methyl-1H-benzimidazole

HRID 1992131Notes

Reaction equation

HRID 1992131 reaction equation
Cl.Cl.[F:3][C:4]1[CH:5]=[C:6]([C:10]2([CH2:16][CH2:17][N:18]3[CH:23]4[CH2:24][CH2:25][CH:19]3[CH2:20][CH:21]([N:26]3[C:30]5[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=5[N:28]=[C:27]3[CH3:35])[CH2:22]4)[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH:7]=[CH:8][CH:9]=1.[F:36][C:37]([F:47])([F:46])[C:38]1[C:42]([C:43]([OH:45])=O)=CNN=1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.[N:64]1(OC(N(C)C)=[N+](C)C)[C:68]2N=CC=[CH:72][C:67]=2N=N1>CN(C)C=O>[F:3][C:4]1[CH:5]=[C:6]([C:10]2([CH2:16][CH2:17][N:18]3[CH:23]4[CH2:24][CH2:25][CH:19]3[CH2:20][CH:21]([N:26]3[C:30]5[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=5[N:28]=[C:27]3[CH3:35])[CH2:22]4)[CH2:11][CH2:12][N:13]([C:43]([C:42]3[C:38]([C:37]([F:36])([F:46])[F:47])=[CH:72][CH:67]=[CH:68][N:64]=3)=[O:45])[CH2:14][CH2:15]2)[CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 686759471-(8-{2-[4-(3-fluorophenyl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole dihydrochlorideHCID 178524805HCID 178524805, compound2×

Product 1

HCID 686757521-{8-[2-(4-(3-fluorophenyl)-1-{[3-(trifluoromethyl)pyridin-2-yl]carbonyl}piperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-2-methyl-1H-benzimidazoleYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(8-{2-[4-(3-fluoro phenyl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole dihydrochloride II (130 mg, 0.25 mmol, 1 eq.) in dimethylformamide (4 mL) was added 3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid, 1a, (50 mg, 0.27 mmol, 1 eq.) and N,N-diisopropylethyl amine (180 μL, 1.0 mmol, 4 eq.). After stirring at RT for several min, O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyl-uroniumhexafluorophosphate (95 mg, 0.25 mmol, 1 eq.) was added and the reaction was stirred for 2 h. The mixture was partitioned between dichloromethane and satd. aq. NaHCO3. The organic layer was dried and concentrated and the residue was purified by prep. HPLC (Method Y) to provide 1-{8-[2-(4-(3-fluorophenyl)-1-{[3-(trifluoromethyl)pyridin-2-yl]carbonyl}piperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-2-methyl-1H-benzimidazole 1 as a white solid (30 mg, 20% yield).

Workup

  1. additionwas added
  2. customThe mixture was partitioned between dichloromethane
  3. customThe organic layer was dried
  4. concentrationconcentrated
  5. customthe residue was purified by prep

Sources & evidence

ORD record
ord-7bdd7f0580544d94b3a960552f0f5e9c
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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