Acetylene → HCID 54559261, compound

HRID 2299899Notes

Reaction equation

HRID 2299899 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:32][CH:33]=[C:34]([CH3:36])[CH3:35])[CH:9]2[CH2:14][CH2:13][N:12]([C:15]([C@@H:17]([NH:22][C:23]([N:25]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)=[O:24])[CH2:18][CH:19]([CH3:21])[CH3:20])=[O:16])[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:44]([C:46]1([OH:52])[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]1)#[CH:45].C#C>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[OH:52][C:46]1([C:44]#[C:45][C:2]2[CH:7]=[CH:6][C:5]([N:8]([CH2:32][CH:33]=[C:34]([CH3:36])[CH3:35])[CH:9]3[CH2:14][CH2:13][N:12]([C:15]([C@@H:17]([NH:22][C:23]([N:25]4[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]4)=[O:24])[CH2:18][CH:19]([CH3:20])[CH3:21])=[O:16])[CH2:11][CH2:10]3)=[CH:4][CH:3]=2)[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]1

Participants

7

Reactant 4

HCID 6326AcetyleneHCID 65251-EthynylcyclohexanolHCID 8471TriethylamineHCID 53642920HCID 53642920, compound

Product 1

HCID 54559261HCID 54559261, compoundYield 39.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 8028TetrahydrofuranSolvent

Procedure

(S)-Azepane-1-carboxylic acid (1-{4-[(4-iodo-phenyl)-(3-methyl-but-2-enyl)-amino]-piperidine-1-carbonyl}-3-methyl-butyl)-amide (0.50 g, 0.49 mmol) was dissolved in THF (4 mL), treated with triethylamine (0.34 mL, 2.45 mmol), 1-ethynyl-1-cyclohexanol (94 RL, 0.74 mmol), Pd(Ph3P)2Cl2 (34 mg, 0.049 mmol), and cuprous iodide (4.8 mg, 0.028 mmol). The reaction was stirred overnight at room temperature, then heated to 40° C. overnight. Another 1.5 equivalents of the acetylene, 0.1 equivalents of Pd(Ph3P)2Cl2, and 0.05 equivalents of cuprous iodide were added and the reaction was heated to 40° C. overnight. The reaction was then concentrated in vacuo and chromatographed on silica gel eluting with 4:3 hexane/EtOAc to give 116 mg (39%) of the desired product.

Workup

  1. temperatureheated to 40° C. overnight
  2. temperaturethe reaction was heated to 40° C. overnight
  3. concentrationThe reaction was then concentrated in vacuo
  4. customchromatographed on silica gel eluting with 4:3 hexane/EtOAc

Sources & evidence

ORD record
ord-ae299a7416c44a7a8bc2132398701266
Source dataset
uspto-grants-2002_12
Patent number
US06495715B2

Reaction notes

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