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

HRID 81568

反応式

HRID 81568 の反応式
[C:1]([O:5][C:6](=[O:27])[NH:7][C:8]1[C@:9]([CH3:26])([C:22]([F:25])([F:24])[F:23])[O:10][CH2:11][C@:12](C2C=CC=C(N)C=2)([CH3:14])[N:13]=1)([CH3:4])([CH3:3])[CH3:2].[Br:28][C:29]1[CH:30]=[CH:31][C:32]([C:35]([OH:37])=O)=[N:33][CH:34]=1.[CH2:38](Cl)[CH2:39]Cl.[CH:42]1C=N[C:45]2N(O)N=[N:50][C:44]=2[CH:43]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([O:5][C:6](=[O:27])[NH:7][C:8]1[C@:9]([CH3:26])([C:22]([F:25])([F:24])[F:23])[O:10][CH:11]([C:39]2[CH:38]=[CH:42][CH:43]=[C:44]([NH:50][C:35]([C:32]3[CH:31]=[CH:30][C:29]([Br:28])=[CH:34][N:33]=3)=[O:37])[CH:45]=2)[C@@H:12]([CH3:14])[N:13]=1)([CH3:4])([CH3:2])[CH3:3]

参加物

7

反応物 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 6085445-Bromopyridine-2-carboxylic acidHCID 67979198[(2R*,5R*)-5-(3-amino-phenyl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester

生成物 1

HCID 86716533((2R*,5R*)-6-{3-[(5-bromo-pyridine-2-carbonyl)-amino]-phenyl}-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl)-carbamic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
25 °C

実験手順

To a solution of [(2R*,5R*)-5-(3-amino-phenyl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester (0.1 g, 0.253 mmol) in DMF (2.5 ml) was added 5-bromo-pyridine-2-carboxylic acid (78 mg, 0.379 mmol), EDC (0.074 g, 0.379 mmol), HOAt (0.053 g, 0.379 mmol) and DIPEA (0.083 g, 0.632 mmol) and the reaction mixture was stirred for 2 h at 25° C. After evaporation of the DMF the residue was taken up in NaH2PO4 solution and extracted with EtOAc. Combined organic layers were washed with 5% NaHCO3 solution and brine, dried over MgSO4, filtered and concentrated. The crude product was crystallized from diisopropylether to provide the title compound as a white crystalline solid: TLC (hexane/EtOAc 1:1): Rf=0.61; HPLC RtH5=1.565 min; 1H NMR (360 MHz, CDCl3): ): δ 11.01 (s, 1H), 9.92 (s, 1H), 8.71 (dd, 1H), 8.21 (d, 1H), 8.10 (dd, 1H), 7.87 (s, 1H), 7.73 (d, 1H), 7.46 (t, 1H), 7.18 (d, 1H), 4.10 (m, 2H), 1.75 (s, 3H), 1.67 (s, 3H), 1.58 (s, 9H); ESIMS: 571, 573 [(M+H)+].

後処理

  1. customAfter evaporation of the DMF the residue
  2. extractionextracted with EtOAc
  3. washCombined organic layers were washed with 5% NaHCO3 solution and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was crystallized from diisopropylether

出典と根拠

ORDレコード
ord-411d0a127ceb45099ba00b50725b2290
出典データセット
uspto-grants-2014_09
特許番号
US08846658B2

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