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

反応式

HRID 1246776 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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

後処理

  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

出典と根拠

ORDレコード
ord-f1830a2f675141d984f02a00daa750d8
出典データセット
uspto-grants-2006_10
特許番号
US07129242B2

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