Ammonia → HCID 58727924, compound

HRID 1992086Notes

Reaction equation

HRID 1992086 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.[N:33]1[CH:38]=[CH:37][CH:36]=[C:35]2[C:39](O[C:42](=[O:43])[C:34]=12)=[O:40].C([N:46](CC)CC)C.N.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[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)[CH2:18][CH2:19][N:20]([C:42]([C:34]5[N:33]=[CH:38][CH:37]=[CH:36][C:35]=5[C:39]([NH2:46])=[O:40])=[O:43])[CH2:21][CH2:22]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

Participants

7

Reactant 5

HCID 222AmmoniaHCID 8471TriethylamineHCID 69688Furo[3,4-b]pyridine-5,7-dioneHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 587278272-Methyl-1-{8-[2-(4-phenyl-4-piperidinyl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole

Product 1

HCID 58727924HCID 58727924, compoundYield 73.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

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 (51 mg, 0.12 mmol) in dichloro-methane (4 mL) was added 2,3-pyridinedicarboxylic anhydride (18 mg, 0.12 mmol) and triethylamine (17 μL, 0.12 mmol). The resulting mixture was stirred for 2 hours at ambient temperature before addition of ammonia (1 mL, 0.5 M in dioxane) and 47 mg of HATU. The reaction mixture was then stirred for another 2 hours. After being diluted with methylene chloride and washed with saturated sodium bicarbonate solution, the organic phase was dried over anhydrous sodium sulfate. Evaporation of the solvent and purification by flash chromatography afforded 2-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]nicotinamide as a foam (51 mg, 69%). 1H NMR (300 MHz, CDCl3) δ 8.63-8.61 (m, 1H), 8.17 (d, J=6.8 Hz, 1H), 7.66-7.64 (m, 2H), 7.38-7.33 (m, 3H), 7.30-7.22 (m, 4H), 7.20-7.10 (m, 2H), 5.79 (s, 1H), 4.61-4.55 (m, 1H), 4.27-4.22 (m, 1H), 3.40-3.08 (m, 5H), 2.54 (s, 3H), 2.47-2.33 (m, 3H), 2.19-2.15 (m, 1H), 1.97-1.80 (m, 10H), 1.63-1.61 (m, 2H). HRMS m/z (M+H)+ calcd: 577.3291, obsd: 577.3286.

Workup

  1. washwashed with saturated sodium bicarbonate solution
  2. dry with materialthe organic phase was dried over anhydrous sodium sulfate
  3. customEvaporation of the solvent and purification by flash chromatography

Sources & evidence

ORD record
ord-27ec6eac996d49dbb0b0eeec45fbce0c
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

Loading…