1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-Chloro-5-({7-[(2E)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)but-2-enoyl]-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-yl}amino)phenol

HRID 38609

반응식

HRID 38609 반응식
Br[CH2:2]/[CH:3]=[CH:4]/[C:5]([OH:7])=O.Cl.[CH:9]12[O:16][CH:13]([CH2:14][CH2:15]1)[CH2:12][NH:11][CH2:10]2.CCN(C(C)C)C(C)C.Cl.[Cl:27][C:28]1[CH:29]=[C:30]([OH:48])[CH:31]=[C:32]([NH:34][C:35]2[C:36]3[C:43]4[CH2:44][CH2:45][NH:46][CH2:47][C:42]=4[S:41][C:37]=3[N:38]=[CH:39][N:40]=2)[CH:33]=1.CCN=C=NCCCN(C)C>C(Cl)Cl.O>[Cl:27][C:28]1[CH:29]=[C:30]([OH:48])[CH:31]=[C:32]([NH:34][C:35]2[C:36]3[C:43]4[CH2:44][CH2:45][N:46]([C:5](=[O:7])/[CH:4]=[CH:3]/[CH2:2][N:11]5[CH2:10][CH:9]6[O:16][CH:13]([CH2:14][CH2:15]6)[CH2:12]5)[CH2:47][C:42]=4[S:41][C:37]=3[N:38]=[CH:39][N:40]=2)[CH:33]=1

참가 물질

8

반응물 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531Diisopropylethylamine2회HCID 64364114-Bromocrotonic acidHCID 219835368-Oxa-3-aza-bicyclo(3.2.1)octane hydrochlorideHCID 668500883-Chloro-5-(5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-ylamino)phenol hydrochloride

생성물 1

HCID 252209953-Chloro-5-({7-[(2E)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)but-2-enoyl]-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-yl}amino)phenol수율 38.3%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

(2E)-4-Bromobut-2-enoic acid (168 mg, 0.81 mmol) and 8-oxa-3-azabicyclo[3.2.1]octane hydrochloride (130 mg, 0.87 mmol) were dissolved in DCM (2.0 mL). DIPEA (210 mg, 1.62 mmol) was added, and the mixture was stirred at rt for 2 h. Subsequently, 3-chloro-5-(5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4-ylamino)phenol hydrochloride from Example 65A (200 mg, 0.54 mmol), EDCI (104 mg, 0.54 mmol) and DIPEA (140 mg, 1.08 mmol) were added, and the mixture was stirred at rt overnight. Then, the reaction mixture was diluted with water, and after separation the organic layer was washed with water. The solvent was removed in vacuo, and the crude product was purified by preparative HPLC to yield 106 mg (38%) of the title compound.

후처리

  1. stirringthe mixture was stirred at rt overnight
  2. customafter separation the organic layer
  3. washwas washed with water
  4. customThe solvent was removed in vacuo
  5. customthe crude product was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-7fe8481a264b4bb6bd83a21b1f49cf7b
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524722B2

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