Methylamine → HCID 118599735, compound

HRID 1054182Notes

Reaction equation

HRID 1054182 reaction equation
[CH3:1][NH2:2].[F:3][C:4]1[CH:30]=[CH:29][C:7]2[N:8]([C:16]([C:18]3[CH:19]=[CH:20][C:21]4[O:26][CH2:25][C:24](=[O:27])[NH:23][C:22]=4[CH:28]=3)=[O:17])[CH:9]([CH2:12][C:13](O)=[O:14])[CH2:10][O:11][C:6]=2[CH:5]=1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CCOC(C)=O>[F:3][C:4]1[CH:30]=[CH:29][C:7]2[N:8]([C:16]([C:18]3[CH:19]=[CH:20][C:21]4[O:26][CH2:25][C:24](=[O:27])[NH:23][C:22]=4[CH:28]=3)=[O:17])[CH:9]([CH2:12][C:13]([NH:2][CH3:1])=[O:14])[CH2:10][O:11][C:6]=2[CH:5]=1

Participants

5

Reactant 3

HCID 6329MethylamineHCID 111923Propylphosphonic anhydrideHCID 118599616HCID 118599616, compound2×

Product 1

HCID 118599735HCID 118599735, compoundYield 47.6%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

Methanamine (2 M solution in THF, 259 μL, 0.52 mmol) was added to a stirred suspension of {7-fluoro-4-[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazin-3-yl}acetic acid (Intermediate 15, 40 mg, 0.10 mmol) and TEA (43 μL, 0.31 mmol) in EtOAc (2 mL) at rt. A thick white precipitate was formed. Addition of T3P (50 wt. % in EtOAc, 123 μL, 0.21 mmol) to the mixture resulted in a clear, pale yellow reaction solution. The mixture was stirred at rt over night. EtOAc (10 mL) was added and the mixture was washed with sat. aq. NaHCO3 (5 mL), HCl (1 M, 5 mL) and brine (5 mL), dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (using 5% MeOH in DCM as eluent), dissolved in ACN/water (approx. 5 mL, 1:4) and freeze-dried to give the title compound (19 mg, 46%) as a white solid.

Workup

  1. customA thick white precipitate was formed
  2. customresulted in a clear, pale yellow reaction solution
  3. washthe mixture was washed with sat. aq. NaHCO3 (5 mL), HCl (1 M, 5 mL) and brine (5 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography (using 5% MeOH in DCM as eluent)
  7. dissolutiondissolved in ACN/water (approx. 5 mL, 1:4)
  8. customfreeze-dried

Sources & evidence

ORD record
ord-90c9f52370e64a22a5c9a7a7093ee667
Source dataset
uspto-grants-2016_07
Patent number
US09394291B2

Reaction notes

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