Pyridine → 3-{[6-(azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-5-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]-N-(5-methylpyrazin-2-yl)benzamide

HRID 1011809Notes

Reaction equation

HRID 1011809 reaction equation
ClC(N(C)C)=C(C)C.[N:9]1([C:13]([C:15]2[N:20]=[CH:19][C:18]([O:21][C:22]3[CH:23]=[C:24]([CH:28]=[C:29]([O:31][C@@H:32]([CH3:42])[CH2:33][O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[CH:30]=3)[C:25](O)=[O:26])=[CH:17][CH:16]=2)=[O:14])[CH2:12][CH2:11][CH2:10]1.[NH2:43][C:44]1[CH:49]=[N:48][C:47]([CH3:50])=[CH:46][N:45]=1.N1C=CC=CC=1>C(Cl)Cl>[N:9]1([C:13]([C:15]2[N:20]=[CH:19][C:18]([O:21][C:22]3[CH:23]=[C:24]([CH:28]=[C:29]([O:31][C@@H:32]([CH3:42])[CH2:33][O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:36])[CH3:37])[CH:30]=3)[C:25]([NH:43][C:44]3[CH:49]=[N:48][C:47]([CH3:50])=[CH:46][N:45]=3)=[O:26])=[CH:17][CH:16]=2)=[O:14])[CH2:10][CH2:11][CH2:12]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 3132155-Methylpyrazin-2-amineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 53629685HCID 53629685, compound

Product 1

HCID 536296833-{[6-(azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-5-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]-N-(5-methylpyrazin-2-yl)benzamideYield 22.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-Chloro-N,N,2-trimethyl-1-propenylamine (0.11 mL, 0.80 mmol) was added to a solution of 3-{[6-(azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-5-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]benzoic acid (0.3 g, 0.62 mmol) in DCM (10 mL) and stirred for 1 hour. 2-Amino-5-methylpyrazine (135 mg, 1.23 mmol), then pyridine (0.1 mL, 1.23 mmol), were added and the mixture stirred for a further 30 mins before being reduced in vacuo and partitioned between ethyl acetate (50 mL) and water (50 mL). The aqueous layer was further extracted into ethyl acetate (50 mL) and the combined organics washed with water (50 mL), brine (50 mL), dried (MgSO4), filtered and reduced in vacuo. The crude oil was chromatographed on silica, eluting with 40-100% ethyl acetate in isohexane, to give the desired compound as a colourless oil (82 mg).

Workup

  1. stirringthe mixture stirred for a further 30 mins
  2. custompartitioned between ethyl acetate (50 mL) and water (50 mL)
  3. extractionThe aqueous layer was further extracted into ethyl acetate (50 mL)
  4. washthe combined organics washed with water (50 mL), brine (50 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customThe crude oil was chromatographed on silica
  8. washeluting with 40-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-8e93f50f97bb45b183a55b5f47950cde
Source dataset
uspto-grants-2011_07
Patent number
US07977328B2

Reaction notes

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