Hexylamine → methyl 3-(5-(2-ethyl-4-(hexylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yloxy)-2,2-dimethylpropanoate

HRID 473964Notes

Reaction equation

HRID 473964 reaction equation
[CH2:1]([NH2:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].Cl[C:9]([N:11]1[CH2:16][CH:15]([CH2:17][CH3:18])[O:14][C:13]2[CH:19]=[C:20]([C:23]3[CH:24]=[CH:25][C:26]([O:29][CH2:30][C:31]([CH3:37])([CH3:36])[C:32]([O:34][CH3:35])=[O:33])=[N:27][CH:28]=3)[CH:21]=[CH:22][C:12]1=2)=[O:10].C(N(C(C)C)C(C)C)C>C(Cl)Cl>[CH2:17]([CH:15]1[O:14][C:13]2[CH:19]=[C:20]([C:23]3[CH:24]=[CH:25][C:26]([O:29][CH2:30][C:31]([CH3:37])([CH3:36])[C:32]([O:34][CH3:35])=[O:33])=[N:27][CH:28]=3)[CH:21]=[CH:22][C:12]=2[N:11]([C:9](=[O:10])[NH:7][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH2:16]1)[CH3:18]

Participants

5

Reactant 3

HCID 8102HexylamineHCID 81531DiisopropylethylamineHCID 58577920HCID 58577920, compound

Product 1

HCID 58577908methyl 3-(5-(2-ethyl-4-(hexylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yloxy)-2,2-dimethylpropanoateYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

n-Hexylamine (23.0 μL, 0.173 mmol) was added dropwise to a solution of methyl 3-(5-(4-(chlorocarbonyl)-2-ethyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yloxy)-2,2-dimethylpropanoate B-11 (50.0 mg, 0.115 mmol) and N-ethyl-N,N-diisopropylamine (40.2 μL, 0.231 mmol) in anhydrous methylene chloride (1.10 mL) at 0° C. under an atmosphere of argon. The reaction mixture was slowly warmed to room temperature and stirred for 8 h, then sequentially diluted with methylene chloride (30 mL), quenched with an aqueous pH 7 phosphate buffer solution (15 mL) and decanted. The aqueous layer was extracted with methylene chloride (3×30 mL); the combined extracts were successively washed with an aqueous pH 7 phosphate buffer solution (20 mL), brine (20 mL), dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure. Crude methyl 3-(5-(2-ethyl-4-(hexylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yloxy)-2,2-dimethylpropanoate B-12 (55.2 mg, Yield=96%) was obtained as a light tan solid and was used for the next step without further purification. MS (ESI) [M+1]+ 498.

Workup

  1. customquenched with an aqueous pH 7 phosphate buffer solution (15 mL)
  2. customdecanted
  3. extractionThe aqueous layer was extracted with methylene chloride (3×30 mL)
  4. washthe combined extracts were successively washed with an aqueous pH 7 phosphate buffer solution (20 mL), brine (20 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-525cd680396c4525a3a401d94344e4d0
Source dataset
uspto-grants-2014_01
Patent number
US08637507B2

Reaction notes

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