Triethylamine → (5-(2-Chlorobenzoyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)(9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undecan-3-yl)methanone

HRID 1808371Notes

Reaction equation

HRID 1808371 reaction equation
Cl.[N:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:29][CH2:28][C:11]3([CH2:16][CH2:15][N:14]([C:17]([C:19]4[S:27][C:26]5[CH2:25][CH2:24][NH:23][CH2:22][C:21]=5[CH:20]=4)=[O:18])[CH2:13][CH2:12]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[Cl:37][C:38]1[CH:46]=[CH:45][CH:44]=[CH:43][C:39]=1[C:40](Cl)=[O:41]>ClCCl.CN(C)C=O>[Cl:37][C:38]1[CH:46]=[CH:45][CH:44]=[CH:43][C:39]=1[C:40]([N:23]1[CH2:24][CH2:25][C:26]2[S:27][C:19]([C:17]([N:14]3[CH2:15][CH2:16][C:11]4([CH2:28][CH2:29][N:8]([C:5]5[CH:6]=[CH:7][N:2]=[CH:3][CH:4]=5)[CH2:9][CH2:10]4)[CH2:12][CH2:13]3)=[O:18])=[CH:20][C:21]=2[CH2:22]1)=[O:41]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 691102-Chlorobenzoyl chlorideHCID 68507109(9-(Pyridin-4-yl)-3,9-diazaspiro[5.5]undecan-3-yl)(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)methanone hydrochloride

Product 1

HCID 46897096(5-(2-Chlorobenzoyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)(9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undecan-3-yl)methanone

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

(9-(Pyridin-4-yl)-3,9-diazaspiro[5.5]undecan-3-yl)(4,5,6,7-tetrahydrothieno[3,2-c]-pyridin-2-yl)methanone hydrochloride (0.089 g, 0.208 mmol) was dissolved in dichloromethane (4 ml) and N,N-dimethylformamide (1 ml), and triethylamine (0.072 ml, 0.52 mmol) was added. The mixture was cooled with an ice bath, and 2-chlorobenzoyl chloride (0.036 g, 0.208 mmol), dissolved in dichloromethane (4 ml), was added slowly at 0° C. The cooling bath was removed and the reaction mixture was stirred for 15 h at RT. Saturated sodium hydrogen carbonate solution (15 ml) was then added and the phases were separated. The aqueous phase was extracted with dichloromethane (25 ml) and the combined organic phases were washed with saturated NaCl solution (10 ml) and saturated sodium chloride solution (10 ml), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, ethyl acetate/methanol/ammonia (25% aq.), 500:100:1). Yield: 80 mg (72%). MS, Rt=3.0 min; m/z=535.2 [MH]+

Workup

  1. temperatureThe mixture was cooled with an ice bath
  2. additionwas added slowly at 0° C
  3. customThe cooling bath was removed
  4. additionSaturated sodium hydrogen carbonate solution (15 ml) was then added
  5. customthe phases were separated
  6. extractionThe aqueous phase was extracted with dichloromethane (25 ml)
  7. washthe combined organic phases were washed with saturated NaCl solution (10 ml) and saturated sodium chloride solution (10 ml)
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by column chromatography (silica gel, ethyl acetate/methanol/ammonia (25% aq.), 500:100:1)

Sources & evidence

ORD record
ord-e0e639de3466476a8cac77d4d45dffd4
Source dataset
uspto-grants-2013_01
Patent number
US08357717B2

Reaction notes

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