1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → [4-(3-Dimethylamino-propyl)piperazin-1-yl]-(4-{4-[4-(tetrahydropyran-4-sulfonyl)phenyl]pyrimidin-2-ylamino}phenyl)methanone

HRID 1246776

반응식

HRID 1246776 반응식
[O:1]1[CH2:6][CH2:5][CH:4]([S:7]([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C:23]4[CH:31]=[CH:30][C:26]([C:27]([OH:29])=O)=[CH:25][CH:24]=4)[N:17]=3)=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH2:3][CH2:2]1.[CH3:32][N:33]([CH2:35][CH2:36][CH2:37][N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1)[CH3:34].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>C1COCC1.C(Cl)Cl>[CH3:34][N:33]([CH3:32])[CH2:35][CH2:36][CH2:37][N:38]1[CH2:39][CH2:40][N:41]([C:27]([C:26]2[CH:25]=[CH:24][C:23]([NH:22][C:18]3[N:17]=[C:16]([C:13]4[CH:12]=[CH:11][C:10]([S:7]([CH:4]5[CH2:3][CH2:2][O:1][CH2:6][CH2:5]5)(=[O:8])=[O:9])=[CH:15][CH:14]=4)[CH:21]=[CH:20][N:19]=3)=[CH:31][CH:30]=2)=[O:29])[CH2:42][CH2:43]1

참가 물질

7

반응물 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 27362341-[3-(Dimethylamino)propyl]piperazineHCID 219059944-{4-[4-(Tetrahydro-pyran-4-sulfonyl)-phenyl]-pyrimidin-2-ylamino}-benzoic acid

생성물 1

HCID 21906004[4-(3-Dimethylamino-propyl)piperazin-1-yl]-(4-{4-[4-(tetrahydropyran-4-sulfonyl)phenyl]pyrimidin-2-ylamino}phenyl)methanone수율 22.2%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

4-{4-[4-(Tetrahydropyran-4-sulfonyl)-phenyl]pyrimidin-2-ylamino}benzoic acid 4 (0.26 g, 0.6 mmol) was dissolved in THF (5 mL). To this solution was added 1-(N,N-dimethylaminopropyl)piperazine (0.130 g), EDCI (0.136 g), and HOBt (0.096 g). The mixture was stirred 12 h. The mixture was then diluted with CH2Cl2 (20 mL) and washed with 2% NaOH (aq, 30 mL), water (30 mL), and then brine (30 mL). The organic layer was dried (Na2SO4), filtered, and concentrated. The crude solid was subjected to preparative HPLC (20–70 acetonitrile/water gradient, 20 min). The desired fractions were concentrated to remove most of the acetonitrile, and then the aqueous mixture was extracted with CH2Cl2/2% NaOH (aq). The organic layer was dried (Na2SO4), filtered, and concentrated to afford [4-(3-dimethylamino-propyl)piperazin-1-yl]-(4-{4-[4-(tetrahydropyran-4-sulfonyl)phenyl]pyrimidin-2-ylamino}phenyl)methanone 5 (0.079 g, 22%): HPLC Retention Time; 7.93 min. (Method B) M+1=593.3

후처리

  1. washwashed with 2% NaOH (aq, 30 mL), water (30 mL)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customwas subjected to preparative HPLC (20–70 acetonitrile/water gradient, 20 min)
  6. concentrationThe desired fractions were concentrated
  7. customto remove most of the acetonitrile
  8. extractionthe aqueous mixture was extracted with CH2Cl2/2% NaOH (aq)
  9. dry with materialThe organic layer was dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated

출처 및 근거

ORD 기록
ord-f1830a2f675141d984f02a00daa750d8
출처 데이터셋
uspto-grants-2006_10
특허 번호
US07129242B2

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