Water → (-)-(cis)-N-(7-cyano-8,12-difluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)-2,2,2-trifluoroacetamide

HRID 1668360ノート

反応式

HRID 1668360 の反応式
Br[C:2]1[C:28]([F:29])=[CH:27][C:5]2[O:6][C:7]3[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:8]=3[C@H:9]3[C@H:14]([NH:15][C:16](=[O:21])[C:17]([F:20])([F:19])[F:18])[CH2:13][CH2:12][CH2:11][N:10]3[C:4]=2[CH:3]=1.[C:30]([Cu])#[N:31].CN1C(=O)CCC1.O>C(OCC)(=O)C.[Cu]I>[C:30]([C:2]1[C:28]([F:29])=[CH:27][C:5]2[O:6][C:7]3[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:8]=3[C@H:9]3[C@H:14]([NH:15][C:16](=[O:21])[C:17]([F:20])([F:18])[F:19])[CH2:13][CH2:12][CH2:11][N:10]3[C:4]=2[CH:3]=1)#[N:31]

参加物

7

反応物 4

HCID 962WaterHCID 13387N-methyl-2-pyrrolidoneHCID 86619616(-)-(cis)-N-(7-bromo-8,12-difluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)-2,2,2-trifluoroacetamideHCID 178418546HCID 178418546、化合物

生成物 1

HCID 86619617(-)-(cis)-N-(7-cyano-8,12-difluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)-2,2,2-trifluoroacetamide収率 59.7%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
180 °C

実験手順

A mixture of 2.74 g (5.74 mmol) of (−)-(cis)-N-(7-bromo-8,12-difluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)-2,2,2-trifluoroacetamide, CuCN (1.3 g, 14.3 mmol), CuI (0.123 g, 0.57 mmol) and NMP (25 mL) was stirred in a microwave for 20 min. at 180° C., 300 Watt with cooling. After cooling down, the reaction mixture was poured into water (500 mL). The precipitate, containing product and salts, was redissolved in ethyl acetate and the salts were filtered off. The organic layer was washed with NH4OH-solution, water, and brine, dried, and concentrated to give the crude compound which was crystallized to give the title compound (1.45 g, 59%). 1H-NMR (400 MHz, DMSO) 1.60-1.86 (m, 3H), 2.01 (m, 1H), 3.15 (m, 1H), 3.86 (m, 1H), 4.133 (d, J=10.0, 1H), 4.35 (m, 1H), 7.00 (m, 1H), 7.03 (m, 1H), 7.44 (d, J=7.7, 1H), 7.6 (d, J=6.3, 1H), 9.23 (br-d, J=7.8, 1H). (m/z)=424 (M+H)+.

後処理

  1. temperature300 Watt with cooling
  2. temperatureAfter cooling down
  3. additionThe precipitate, containing product and salts
  4. filtrationthe salts were filtered off
  5. washThe organic layer was washed with NH4OH-solution, water, and brine
  6. customdried
  7. concentrationconcentrated
  8. customto give the crude compound which
  9. customwas crystallized

出典と根拠

ORDレコード
ord-2ee863f7a7354cff859c805986182d36
出典データセット
uspto-grants-2011_08
特許番号
US07989442B2

反応ノート

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