1,2-Dichloroethane → (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

HRID 81530

反応式

HRID 81530 の反応式
[C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[CH2:9][O:10][CH2:11][C:12]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([N:22]=[N+]=[N-])[CH:17]=2)([CH2:14][F:15])[N:13]=1)([CH3:4])([CH3:3])[CH3:2].C(OC(=O)NC1COCC(C2C=CC=C(N)C=2)(CF)N=1)(C)(C)C.[Br:49][C:50]1[CH:51]=[CH:52][C:53]([C:56](O)=[O:57])=[N:54][CH:55]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C([O-])(O)=O.[Na+]>CCOC(C)=O.[Pd].CC([O-])=O.CC([O-])=O.[Pb+2].ClCCl.C(N(CC)CC)C>[C:1]([O:5][C:6](=[O:25])[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:56]([C:53]3[CH:52]=[CH:51][C:50]([Br:49])=[CH:55][N:54]=3)=[O:57])[CH:17]=2)([CH2:14][F:15])[N:13]=1)([CH3:4])([CH3:3])[CH3:2]

参加物

11

反応物 6

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 6085445-Bromopyridine-2-carboxylic acidHCID 66665608[5-(3-amino-phenyl)-5-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl esterHCID 86650252HCID 86650252、化合物

生成物 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

試薬・触媒・溶媒 4

HCID 131709914Lindlars catalyst触媒HCID 6344Dichloromethane溶媒2 回HCID 8471Triethylamine溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of [5-(3-azido-phenyl)-5-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester (56 mg, 0.161 mmol) in 2 ml of EtOAc was hydrogenated in the presence of Lindlar catalyst (11 mg) for 3 h. The mixture was filtered through Celite, and the filtrate was evaporated. The crude [5-(3-amino-phenyl)-5-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester (50 mg, 0.155 mmol) was taken up in 2 ml of dichloromethane. A mixture of 5-bromo-pyridine-2-carboxylic acid (34.4 mg, 0.170 mmol), HOBT (30.9 mg, 0.17 mmol) and EDC (32.6 mg, 0.17 mmol) in 2 ml of dichloromethane was added, followed by the addition of triethylamine (0.054 ml). The mixture was stirred for 4 h, treated with 5% aqueous NaHCO3 solution and extracted twice with dichloromethane. The organic phase was dried with MgSO4 and evaporated. The residue was chromatographed on silica gel (EtOAc/cyclohexane=1:4) to yield the title compound. TLC (hexane/EtOAc=3:1): Rf=0.16; HPLC: RtH1=2.763 min; 1H-NMR (400 MHz, CDCl3): 9.80 (br, 1H), 8.60 (d, 1H), 8.11 (d, 1H), 7.98 (d, 1H), 7.77 (br, 1H), 7.73 (d, 1H), 7.33 (br, 1H), 7.15 (d, 1H), 4.75-3.65 (m, 6H), 1.60 (br; minor rotamer tBu), 1.42 (br; major rotamer tBu); MS: 507, 509 [(M+H)+].

後処理

  1. filtrationThe mixture was filtered through Celite
  2. customthe filtrate was evaporated
  3. additionwas added
  4. extractionextracted twice with dichloromethane
  5. dry with materialThe organic phase was dried with MgSO4
  6. customevaporated
  7. customThe residue was chromatographed on silica gel (EtOAc/cyclohexane=1:4)

出典と根拠

ORDレコード
ord-81927f34ed3e4104a2d3b10b0c221e10
出典データセット
uspto-grants-2014_09
特許番号
US08846658B2

関連ノート

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