1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 7-{(2E)-4-[tert-Butyl(methyl)amino]but-2-enoyl}-4-[(3-chloro-4-fluorophenyl)amino]-5,6,7,8-tetrahydrothieno[2,3-b:5,4-c']dipyridine-3-carbonitrile

HRID 38625

反応式

HRID 38625 の反応式
Br[CH2:2]/[CH:3]=[CH:4]/[C:5]([OH:7])=O.[C:8]([NH:12][CH3:13])([CH3:11])([CH3:10])[CH3:9].CCN(C(C)C)C(C)C.[Cl:23][C:24]1[CH:25]=[C:26]([NH:31][C:32]2[C:37]([C:38]#[N:39])=[CH:36][N:35]=[C:34]3[S:40][C:41]4[CH2:42][NH:43][CH2:44][CH2:45][C:46]=4[C:33]=23)[CH:27]=[CH:28][C:29]=1[F:30].CCN=C=NCCCN(C)C>C(Cl)Cl.O>[C:8]([N:12]([CH3:13])[CH2:2]/[CH:3]=[CH:4]/[C:5]([N:43]1[CH2:44][CH2:45][C:46]2[C:33]3[C:34]([S:40][C:41]=2[CH2:42]1)=[N:35][CH:36]=[C:37]([C:38]#[N:39])[C:32]=3[NH:31][C:26]1[CH:27]=[CH:28][C:29]([F:30])=[C:24]([Cl:23])[CH:25]=1)=[O:7])([CH3:11])([CH3:10])[CH3:9]

参加物

8

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531Diisopropylethylamine2 回HCID 84552N-Methyl-tert-butylamineHCID 64364114-Bromocrotonic acidHCID 581169284-[(3-Chloro-4-fluorophenyl)amino]-5,6,7,8-tetrahydrothieno[2,3-b:5,4-c']dipyridine-3-carbonitrile

生成物 1

HCID 581169547-{(2E)-4-[tert-Butyl(methyl)amino]but-2-enoyl}-4-[(3-chloro-4-fluorophenyl)amino]-5,6,7,8-tetrahydrothieno[2,3-b:5,4-c']dipyridine-3-carbonitrile収率 38.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

(2E)-4-Bromobut-2-enoic acid (100 mg, 0.61 mmol) and tert-butyl methylamine (60 mg, 0.67 mmol) were dissolved in DCM (3.0 mL). DIPEA (94 mg, 0.73 mmol) was added, and the mixture was heated overnight to 50° C. After cooling to rt, the compound of Example 55A (75 mg, 0.21 mmol), DCM (1.0 mL), EDCI (48 mg, 0.25 mmol) and DIPEA (32 mg, 0.25 mmol) were added, and the mixture was stirred at rt overnight. Subsequently, it was diluted with water, and the mixture was extracted three times with DCM. The combined organic layers were dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by preparative HPLC to yield 41 mg (37%) of the title compound.

後処理

  1. temperaturethe mixture was heated overnight to 50° C
  2. extractionthe mixture was extracted three times with DCM
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. customthe solvent was removed in vacuo
  5. customThe crude product was purified by preparative HPLC

出典と根拠

ORDレコード
ord-f403827c0887475ab55fda7d5929c797
出典データセット
uspto-grants-2013_09
特許番号
US08524722B2

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