Trifluoroacetic acid → 1-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-3-[4-(5-morpholin-4-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)-piperidin-1-yl]-propan-2-ol

HRID 586734ノート

反応式

HRID 586734 の反応式
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:22]3[C:17](=[CH:18][N:19]=[C:20]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)[CH:21]=3)[NH:16][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.[CH3:36][S:37]([N:40]1[CH2:45][CH2:44][C:43]2[N:46]([CH2:59][CH:60]3[CH2:62][O:61]3)[N:47]=[C:48]([C:49]3[CH:54]=[CH:53][C:52]([C:55]([F:58])([F:57])[F:56])=[CH:51][CH:50]=3)[C:42]=2[CH2:41]1)(=[O:39])=[O:38]>C(Cl)Cl>[NH3:8].[CH3:36][S:37]([N:40]1[CH2:45][CH2:44][C:43]2[N:46]([CH2:59][CH:60]([OH:61])[CH2:62][N:8]3[CH2:9][CH2:10][CH:11]([C:14]4[C:22]5[C:17](=[CH:18][N:19]=[C:20]([N:23]6[CH2:24][CH2:25][O:26][CH2:27][CH2:28]6)[CH:21]=5)[NH:16][CH:15]=4)[CH2:12][CH2:13]3)[N:47]=[C:48]([C:49]3[CH:50]=[CH:51][C:52]([C:55]([F:56])([F:57])[F:58])=[CH:53][CH:54]=3)[C:42]=2[CH2:41]1)(=[O:39])=[O:38]

参加物

6

反応物 3

HCID 6422Trifluoroacetic acidHCID 120720315-methanesulfonyl-1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridineHCID 691828124-(5-Morpholin-4-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)-piperidine-1-carboxylic acid tert-butyl ester

生成物 2

HCID 222AmmoniaHCID 101466241-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-3-[4-(5-morpholin-4-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)-piperidin-1-yl]-propan-2-ol収率 60%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
25 °C

実験手順

4-(5-Morpholin-4-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)-piperidine-1-carboxylic acid tert-butyl ester (180 mg, 0.47 mmol) was dissolved in 3.0 mL of CH2Cl2 and treated with 2.5 mL of trifluoroacetic acid. The reaction mixture was stirred at 25° C. for 1 h before all volatiles were removed. The solid was dissolved in MeOH (20 mL) and neutralized with DOWEX 550A OH anion exchange resin to pH 8. The resin was then filtered off and MeOH was removed under reduced pressure. The residue was dissolved in 2.5 mL of iPrOH and treated with 187 mg (0.47 mmol, 1 eq) of 5-methanesulfonyl-1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine. The reaction was stirred at 85° C. for 3 h before solvent was removed. Column chromatography (silica, 5-10% MeOH/CH2Cl2 then 5-10% (2 N NH3 in MeOH)/CH2Cl2) provided 97 mg (30%) of the title compound. TLC (silica, 5% MeOH/CH2Cl2): Rf=0.25. MS (electrospray): exact mass calculated for C33H40F3N7O4S, 687.28; m/z found, 688.3 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.47 (br s, 1H), 8.44 (d, J=1.0 Hz, 1H), 7.70 and 7.65 (AB pattern, J=8.4 Hz, 4H), 7.03 (d, J=2.1 Hz, 1H), 6.76 (s, 1H), 4.58-4.50 (m, 2H), 4.21-4.00 (m, 3H), 3.90 (t, J=4.5 Hz, 4H), 3.72-3.58 (m, 2H), 3.40 (t, J=4.5 Hz, 4H), 3.10-2.85 (m, 4H), 2.88 (s, 3H), 2.80-2.70 (m, 1H), 2.52-2.41 (m, 3H), 2.20-2.00 (m, 3H), 1.80-1.60 (m, 2H).

後処理

  1. customwere removed
  2. dissolutionThe solid was dissolved in MeOH (20 mL)
  3. filtrationThe resin was then filtered off
  4. customMeOH was removed under reduced pressure
  5. dissolutionThe residue was dissolved in 2.5 mL of iPrOH
  6. stirringThe reaction was stirred at 85° C. for 3 h before solvent
  7. customwas removed

出典と根拠

ORDレコード
ord-05ad0ade24c045d9b09b25794d333637
出典データセット
uspto-grants-2005_08
特許番号
US06936603B2

反応ノート

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