(5-{3-[(5-Bromo-pyridine-2-carbonyl)-amino]-phenyl}-5-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl)-carbamic acid tert-butyl ester → 5-Bromo-pyridine-2-carboxylic acid [3-(5-amino-3-fluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-phenyl]-amide

HRID 81531Notes

Reaction equation

HRID 81531 reaction equation
C(OC(=O)[NH:7][C:8]1[CH2:9][O:10][CH2:11][C:12]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([NH:22][C:23]([C:25]3[CH:30]=[CH:29][C:28]([Br:31])=[CH:27][N:26]=3)=[O:24])[CH:17]=2)([CH2:14][F:15])[N:13]=1)(C)(C)C>Cl.CO>[NH2:7][C:8]1[CH2:9][O:10][CH2:11][C:12]([C:16]2[CH:17]=[C:18]([NH:22][C:23]([C:25]3[CH:30]=[CH:29][C:28]([Br:31])=[CH:27][N:26]=3)=[O:24])[CH:19]=[CH:20][CH:21]=2)([CH2:14][F:15])[N:13]=1

Participants

4

Reactant 1

HCID 66665302(5-{3-[(5-Bromo-pyridine-2-carbonyl)-amino]-phenyl}-5-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl)-carbamic acid tert-butyl ester

Product 1

HCID 581188175-Bromo-pyridine-2-carboxylic acid [3-(5-amino-3-fluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-phenyl]-amide

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Procedure

A solution of (5-{3-[(5-bromo-pyridine-2-carbonyl)-amino]-phenyl}-5-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl)-carbamic acid tert-butyl ester (48 mg, 0.095 mmol) in 2 ml of 3N HCl in MeOH was stirred at 40° C. for 2 h. The mixture was evaporated, and the residue was purified by chromatography on silica gel with a gradient of dichloromethane and 2-10% MeOH/NH4OH (0.5%), yielding the title compound in the form of a colorless foam. TLC (dichloromethane/MeOH/25% aqueous NH4OH=90:9:1): Rf=0.28; HPLC: RtH1=2.755 min; 1H-NMR (400 MHz, CDCl3): 8.58 (d, 1H), 8.10 (d, 1H), 7.96 (dd, 1H), 7.76 (s, 1H), 7.71 (d, 1H), 7.31 (t, 1H), 7.21 (d, 1H), 4.55-4.33 (m, 2H), 4.13-3.95 (m, 3H), 3.65 (d, 1H), 4.0-3.3 (br, NH2); MS: 407, 409 [(M+H)+].

Workup

  1. customThe mixture was evaporated
  2. customthe residue was purified by chromatography on silica gel with a gradient of dichloromethane and 2-10% MeOH/NH4OH (0.5%)

Sources & evidence

ORD record
ord-67e337e531a74546942e303b3ca9f44b
Source dataset
uspto-grants-2014_09
Patent number
US08846658B2

Reaction notes

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