4-Methylmorpholine → HCID 178454216、化合物

HRID 1424187ノート

反応式

HRID 1424187 の反応式
[NH:1]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C@H:2]([C:26](O)=O)[CH2:3][C:4](=[O:25])[NH:5][C:6]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:51][C:52]1[CH:53]=[C:54]([C:59]2[CH:64]=[CH:63][C:62]([C:65]#[N:66])=[C:61]([F:67])[CH:60]=2)[CH:55]=[CH:56][C:57]=1[NH2:58]>C(#N)C>[C:65]([C:62]1[CH:63]=[CH:64][C:59]([C:54]2[CH:55]=[CH:56][C:57]3[NH:58][C:26]([C@@H:2]([NH:1][C:29](=[O:30])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:3][C:4](=[O:25])[NH:5][C:6]([C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=4)([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)[C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=4)=[N:51][C:52]=3[CH:53]=2)=[CH:60][C:61]=1[F:67])#[N:66]

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 11385960Boc-Asn(Trt)-OHHCID 866991143',4'-Diamino-3-fluoro-[1,1'-biphenyl]-4-carbonitrile

生成物 1

HCID 178454216HCID 178454216、化合物収率 60%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a solution of Boc-Asn(Trt)-OH (100.4 mg, 0.2116 mmol) in acetonitrile (2.0 mL) cooled in an ice water bath was added 4-methylmorpholine (0.059 mL, 0.53 mmol) and isobutyl chloroformate (0.027 mL, 0.21 mmol). After stirring for 60 minutes, 3′,4′-diamino-3-fluoro-[1,1-biphenyl]-4-carbonitrile (Preparation 81, 42.7 mg, 0.188 mmol) was added and the mixture allowed to warm to room temperature. After stirring for 18 hours the reaction mixture was concentrated in vacuo and redissolved in acetic acid. After stirring at room temperature for 6.5 hours, the mixture was concentrated in vacuo, redissolved in ethyl acetate, washed with water, 0.5M HCl, and brine. The organic layer was dried over anhydrous magnesium sulphate, filtered, and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with a 0-100% ethyl acetate/hexanes gradient to afford the title compound (75 mg, 60%).

後処理

  1. stirringAfter stirring for 18 hours the reaction mixture
  2. concentrationwas concentrated in vacuo
  3. dissolutionredissolved in acetic acid
  4. stirringAfter stirring at room temperature for 6.5 hours
  5. concentrationthe mixture was concentrated in vacuo
  6. dissolutionredissolved in ethyl acetate
  7. washwashed with water, 0.5M HCl, and brine
  8. dry with materialThe organic layer was dried over anhydrous magnesium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified
  12. washeluting with a 0-100% ethyl acetate/hexanes gradient

出典と根拠

ORDレコード
ord-501c3abc46dc40baa80d7dba3adde223
出典データセット
uspto-grants-2015_01
特許番号
US08927587B2

反応ノート

読み込み中…