Triethylamine → 2-Chloro-N-[(1R)-6-(9-pyridin-4-yl-2,9-diazaspiro[5.5]undecane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide

HRID 1253749Notes

Reaction equation

HRID 1253749 reaction equation
Cl.[CH2:2]1[C:7]2([CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][N:3]1[C:13]([C:15]1[CH:23]=[C:22]2[C:18]([CH2:19][CH2:20][C@H:21]2[NH:24][C:25](=[O:33])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[Cl:32])=[CH:17][CH:16]=1)=[O:14].C(N(CC)CC)C.Cl.Cl[C:43]1[CH:48]=[CH:47][N:46]=[CH:45][CH:44]=1.C([O-])(O)=O.[Na+]>C(O)CCC.C(OCC)(=O)C>[Cl:32][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[C:25]([NH:24][C@H:21]1[C:22]2[C:18](=[CH:17][CH:16]=[C:15]([C:13]([N:3]3[CH2:4][CH2:5][CH2:6][C:7]4([CH2:8][CH2:9][N:10]([C:43]5[CH:48]=[CH:47][N:46]=[CH:45][CH:44]=5)[CH2:11][CH2:12]4)[CH2:2]3)=[O:14])[CH:23]=2)[CH2:19][CH2:20]1)=[O:33]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 818524-Chloropyridine hydrochlorideHCID 516892Sodium BicarbonateHCID 66701068(R)-N-(6-(2,9-Diazaspiro[5.5]undecane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl)-2-chlorobenzamide hydrochloride

Product 1

HCID 469359302-Chloro-N-[(1R)-6-(9-pyridin-4-yl-2,9-diazaspiro[5.5]undecane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamideYield 73%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of (R)—N-(6-(2,9-diazaspiro[5.5]undecane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl)-2-chlorobenzamide hydrochloride (0.491 mmol, 1.0 eq.), triethylamine (5.0 eq.) and 4-chloropyridine hydrochloride (3.0 eq.) in n-butanol (13 ml) was stirred at 110° C. overnight. Ethyl acetate and sat. NaHCO3 solution were added and the aqueous phase was extracted with ethyl acetate a further 4×. The combined organic phases were washed 1× with sat. NaCl solution, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (silica, ethyl acetate/ethanol/ammonia (25% aq) 100:10:1) to obtain the desired product (H-54). Yield: 73%

Workup

  1. extractionthe aqueous phase was extracted with ethyl acetate a further 4×
  2. washThe combined organic phases were washed 1× with sat. NaCl solution
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by column chromatography (silica, ethyl acetate/ethanol/ammonia (25% aq) 100:10:1)

Sources & evidence

ORD record
ord-289d137ec62b4640a7dd717734e802c1
Source dataset
uspto-grants-2013_06
Patent number
US08455475B2

Reaction notes

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