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Acetic Acid → 1-{3-[4-(2-Chloro-6-nitro-phenyl)-piperazin-1-yl]-propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester

HRID 734133
ノート
印刷プレビュー

反応式

HRID 734133 の反応式
C(O[C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([N+:20]([O-:22])=[O:21])=[CH:18][CH:17]=[CH:16][C:15]=2[Cl:23])[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][C:41]2[N:44]([CH2:57][CH2:58]C=O)[N:45]=[C:46]([C:47]3[CH:52]=[CH:51][C:50]([C:53]([F:56])([F:55])[F:54])=[CH:49][CH:48]=3)[C:40]=2[CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][C:41]2[N:44]([CH2:57][CH2:58][CH2:6][N:8]3[CH2:9][CH2:10][N:11]([C:14]4[C:19]([N+:20]([O-:22])=[O:21])=[CH:18][CH:17]=[CH:16][C:15]=4[Cl:23])[CH2:12][CH2:13]3)[N:45]=[C:46]([C:47]3[CH:48]=[CH:49][C:50]([C:53]([F:55])([F:56])[F:54])=[CH:51][CH:52]=3)[C:40]=2[CH2:39]1)=[O:37])([CH3:34])([CH3:32])[CH3:33]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 6

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 587677041-Boc-4-(2-chloro-6-nitrophenyl)piperazineHCID 865848181-(3-Oxo-propyl)-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester

生成物 1

HCID 684630981-{3-[4-(2-Chloro-6-nitro-phenyl)-piperazin-1-yl]-propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester収率 92%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
25 °C

実験手順

4-(2-Chloro-6-nitro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (940 mg, 2.75 mmol) in 10 mL of CH2Cl2 was treated with 5 mL of trifluoroacetic acid and stirred at 25° C. for 1 h. The volatiles were then removed. The residue was taken up in CH2Cl2 (60 mL) and KOH (4 N, 20 mL). The organic layer was separated, dried over Na2SO4, and concentrated. The yellow oil was dissolved in CH2Cl2 and added into the 996 mg (2.35 mmol) of 1-(3-oxo-propyl)-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester. The yellow solution was treated with glacial acetic acid (0.8 mL, 6 eq) and stirred at 25° C. for 1 h. NaBH(OAc)3 (1.5 g, 7.05 mmol) was added and stirred under nitrogen for 2 h. Then saturated NaHCO3 (20 mL) was added and stirred for 30 min, and the layers were separated. The organic extract was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. Column chromatography (silica, 2-5% MeOH/CH2Cl2) afforded 1-{3-[4-(2-chloro-6-nitro-phenyl)-piperazin-1-yl]-propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester as a white solid (1.40 g, 92%). TLC (silica, 5% MeOH/CH2Cl2): Rf=0.3. MS (electrospray): exact mass calculated for C31H36ClF3N6O4, 648.24; m/z found 649.3 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.69 (d, J=8.2 Hz, 1H), 7.60-7.50 (m, 1H), 7.45-7.37 (m, 4H), 7.02 (t, J=8.2 Hz, 1H), 4.58 (br s, 2H), 4.04 (t, J=6.7 Hz, 2H), 3.73-3.65 (m, 2H), 3.05-2.95 (m, 4H), 2.71 (t, J=5.6 Hz, 2H), 2.50-2.35 (m, 4H), 2.30 (t, J=6.8 Hz, 2H), 2.05-1.95 (m, 2H), 1.41 (s, 9H).

後処理

  1. customThe volatiles were then removed
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. dissolutionThe yellow oil was dissolved in CH2Cl2
  6. stirringstirred at 25° C. for 1 h
  7. stirringstirred under nitrogen for 2 h
  8. stirringstirred for 30 min
  9. customthe layers were separated
  10. extractionThe organic extract
  11. washwas washed with brine
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-963cd642fd9d43b0bdd2a189f3ea2a10
出典データセット
uspto-grants-2009_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07589202B2

反応ノート

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