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

反応式

HRID 38609 の反応式
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

参加物

8

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531Diisopropylethylamine2 回HCID 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

生成物 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)phenol収率 38.3%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒

実験手順

(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.

後処理

  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

出典と根拠

ORDレコード
ord-7fe8481a264b4bb6bd83a21b1f49cf7b
出典データセット
uspto-grants-2013_09
特許番号
US08524722B2

関連ノート

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