1,2-Dichloroethane → ((R)-5-{3-Bromo-6-[(5-bromo-pyrimidine-2-carbonyl)-amino]-phenyl}-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-yl)-carbamic acid tert-butyl ester

HRID 81560Notes

Reaction equation

HRID 81560 reaction equation
[C:1]([O:5][C:6](=[O:23])[NH:7][C:8]1[CH2:9][O:10][CH2:11][C@:12]([C:15]2[CH:20]=[C:19]([Br:21])[CH:18]=[C:17](N)[CH:16]=2)([CH3:14])[N:13]=1)([CH3:4])([CH3:3])[CH3:2].[Br:24][C:25]1[CH:26]=[N:27][C:28]([C:31]([OH:33])=O)=[N:29][CH:30]=1.C1C=CC2N(O)N=[N:40]C=2C=1.CCN(C(C)C)C(C)C.C(Cl)CCl>ClCCl>[C:1]([O:5][C:6](=[O:23])[NH:7][C:8]1[CH2:9][O:10][CH2:11][C@:12]([C:15]2[C:16]([NH:40][C:31]([C:28]3[N:29]=[CH:30][C:25]([Br:24])=[CH:26][N:27]=3)=[O:33])=[CH:17][CH:18]=[C:19]([Br:21])[CH:20]=2)([CH3:14])[N:13]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 164629705-Bromopyrimidine-2-carboxylic acidHCID 66665299[(R)-5-(3-Amino-5-bromo-phenyl)-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester

Product 1

HCID 86716532((R)-5-{3-Bromo-6-[(5-bromo-pyrimidine-2-carbonyl)-amino]-phenyl}-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-yl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

[(R)-5-(3-Amino-5-bromo-phenyl)-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester (33 mg, 0.082 mmol), 5-bromo-pyrimidine-2-carboxylic acid (18 mg, 0.090 mmol) and HOBT (16 mg, 0.106 mmol) were dissolved in dichloromethane under N2 at 0° C. DIPEA (10.54 mg, 0.082 mmol) and EDC (17 mg, 0.090 mmol) were added. The mixture was stirred at 0° C. for 10 min, then allowed to warm to room temperature, stirred for 17 h at room temperature, quenched with 1M aqueous KHCO3 solution and extracted with dichloromethane. The organic phase was washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by automated column chromatography (cyclohexane/ethyl acetate) to yield the title compound as a tan foam. MS: 569 [(M+H)+].

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 17 h at room temperature
  3. customquenched with 1M aqueous KHCO3 solution
  4. extractionextracted with dichloromethane
  5. washThe organic phase was washed with water and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by automated column chromatography (cyclohexane/ethyl acetate)

Sources & evidence

ORD record
ord-0729d2db3d904f46982a0785ebbbaada
Source dataset
uspto-grants-2014_09
Patent number
US08846658B2

Reaction notes

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