Hydrochloric Acid → (R)-Pyrrolidin-2-yl((R)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-yl)methanone

HRID 445357

反応式

HRID 445357 の反応式
C(OC([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[C:13]([OH:15])=O)=O)(C)(C)C.[F:16][C:17]([F:35])([F:34])[C:18]1[CH:23]=[CH:22][C:21]([C@@H:24]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:27][CH2:26][NH:25]2)=[CH:20][CH:19]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl>CN(C=O)C.O1CCOCC1.O>[NH:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[C:13]([N:25]1[CH2:26][CH2:27][C:28]2[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=2)[C@H:24]1[C:21]1[CH:22]=[CH:23][C:18]([C:17]([F:16])([F:35])[F:34])=[CH:19][CH:20]=1)=[O:15]

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 688022(2R)-1-[(tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 28293305(R)-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline

生成物 1

HCID 59536406(R)-Pyrrolidin-2-yl((R)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-yl)methanone

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 312751,4-Dioxane溶媒2 回

実験手順

To a stirred mixture of (R)-1-(tert-butoxy-carbonyl)pyrrolidine-2-carboxylic acid (0.078 g, 0.36 mmol), (R)-1-(4-(trifluoro-methyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (0.100 g, 0.36 mmol) and DIEA (0.047 g, 0.36 mmol) in DMF (2 mL) was added HATU (0.14 g, 0.36 mmol). The reaction mixture was continued to stir overnight at RT, hydrolyzed with H2O, extracted with DCM (3×), dried over Na2SO4, concentrated and purified by ISCO (20% EtOAc/hexanes) to give the white solid which was dissolved in p-dioxane (2 mL) and added 1 mL of 4M HCl in p-dioxane. The mixture was continued to stir at RT overnight, concentrated, taken up in H2O, and neutralized by saturated aqueous NaHCO3, and filtered the light yellow solid which was dried by air. MS (ESI, positive ion) m/z: 375 (M+1).

後処理

  1. extractionextracted with DCM (3×)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. custompurified by ISCO (20% EtOAc/hexanes)
  5. customto give the white solid which
  6. concentrationconcentrated
  7. filtrationfiltered the light yellow solid which
  8. customwas dried by air

出典と根拠

ORDレコード
ord-9a93e900122a4fc9b1bab144aa9bc64f
出典データセット
uspto-grants-2013_07
特許番号
US08476297B2

関連ノート

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