Methylamine → 2-{7-Chloro-4-[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazin-3-yl}-N-methylacetamide

HRID 1054189Notes

Reaction equation

HRID 1054189 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:10]([C:11]([C:13]3[CH:23]=[CH:22][C:16]4[O:17][CH2:18][C:19](=[O:21])[NH:20][C:15]=4[CH:14]=3)=[O:12])[CH:9]([CH2:24][C:25]([OH:27])=O)[CH2:8][O:7][C:6]=2[CH:28]=1.[CH3:29][NH2:30].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:10]([C:11]([C:13]3[CH:23]=[CH:22][C:16]4[O:17][CH2:18][C:19](=[O:21])[NH:20][C:15]=4[CH:14]=3)=[O:12])[CH:9]([CH2:24][C:25]([NH:30][CH3:29])=[O:27])[CH2:8][O:7][C:6]=2[CH:28]=1

Participants

5

Reactant 3

HCID 6329MethylamineHCID 111923Propylphosphonic anhydrideHCID 1185996432-(7-chloro-4-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-3-yl)acetic acid2×

Product 1

HCID 1185996182-{7-Chloro-4-[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazin-3-yl}-N-methylacetamideYield 64.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-(7-chloro-4-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-3-yl)acetic acid (Intermediate 22, 38 mg, 0.09 mmol), methanamine (0.236 mL, 0.47 mmol) (2 M solution in THF), and TEA (0.039 mL, 0.28 mmol) in EtOAc (2 mL) was treated with T3P (50 wt. % in EtOAc, 0.112 mL, 0.19 mmol) at rt. The reaction mixture was stirred at rt over night and concentrated. The crude product was purified by preparative HPLC (Kromasil C8 column (10 μm 250×20 ID mm), using a gradient of 20-60% ACN in H2O/ACN/FA 95/5/0.2 buffer, over 20 min with a flow of 19 mL/min, UV detection at 240 nm). Freeze-drying gave the title compound (24 mg, 61%) as a white powder.

Workup

  1. concentrationconcentrated
  2. customThe crude product was purified by preparative HPLC (Kromasil C8 column (10 μm 250×20 ID mm)
  3. customFreeze-drying

Sources & evidence

ORD record
ord-a4c091a3cb8e4794ad4caed3765d5ad0
Source dataset
uspto-grants-2016_07
Patent number
US09394291B2

Reaction notes

Loading…