1,2-Dichloroethane → HCID 58728805, compound

HRID 1992209Notes

Reaction equation

HRID 1992209 reaction equation
[CH:1]1([CH:7]([N:11]2[CH2:16][CH2:15][C:14]([C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([F:43])[CH:38]=3)([CH2:17][CH2:18][N:19]3[C@H:24]4[CH2:25][CH2:26][C@@H:20]3[CH2:21][CH:22]([N:27]3[C:31]5[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=5[N:29]=[C:28]3[CH3:36])[CH2:23]4)[CH2:13][CH2:12]2)[C:8](O)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN.O[N:47]1[C:51]2C=CC=CC=2N=N1.CN1CCOCC1.C(Cl)CCl>C1COCC1.CN(C=O)C.CCOC(C)=O>[CH:1]1([CH:7]([N:11]2[CH2:12][CH2:13][C:14]([C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([F:43])[CH:38]=3)([CH2:17][CH2:18][N:19]3[C@H:20]4[CH2:26][CH2:25][C@@H:24]3[CH2:23][CH:22]([N:27]3[C:31]5[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=5[N:29]=[C:28]3[CH3:36])[CH2:21]4)[CH2:15][CH2:16]2)[C:8]([NH:47][CH3:51])=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 6329MethylamineHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 68677588HCID 68677588, compound

Product 1

HCID 58728805HCID 58728805, compoundYield 36.5%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of cyclohexyl(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-1-yl)acetic acid (22.0 mg, 0.037 mmol), methylamine (0.056 mL of a 2M solution in THF, 0.11 mmol), N-hydroxybenzotriazole (10.1 mg, 0.075 mmol) and N-methylmorpholine (0.10 mL, 0.094 mmol) in 1 mL DMF was added EDC (14 mg, 0.075 mmol). The reaction mixture was stirred for 24 h, then diluted with 4:1 EtOAc:hex and washed with saturated aqueous NaHCO3, dried (Na2SO4) and chromatographed (5% (2M NH3/MeOH) in CHCl3) to provide 2-cyclohexyl-2-(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-1-yl)-N-methylacetamide (8.1 mg, 36%) as a solid. 1H NMR (400 MHz, CDCl3), δ 7.66 (m, 1H), 7.33-7.27 (m, 2H), 7.20-7.11 (m, 2H), 7.05 (m, 1H), 6.98 (m, 1H), 6.90 (m, 1H), 4.64 (m, 1H), 3.33-3.20 (m, 2H), 2.80 (d, 3H, J=4.9 Hz), 2.59 (s, 3H), 2.47-0.79 (m, 27H); ESI-MS 600 (M+H).

Workup

  1. washhex and washed with saturated aqueous NaHCO3
  2. dry with materialdried (Na2SO4)
  3. customchromatographed (5% (2M NH3/MeOH) in CHCl3)

Sources & evidence

ORD record
ord-4123125192294a57a03a16fbe013cec1
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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