Ammonium Chloride → HCID 24968236、化合物

HRID 216669

反応式

HRID 216669 の反応式
CC(C)([O-])C.[K+].CO[C:9](=[O:21])[C:10]([C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)=O.[CH3:22][N:23]([CH2:25][C:26]1[CH:27]=[CH:28][C:29]2[N:30]([C:32]([CH2:35][C:36]([NH2:38])=[O:37])=[CH:33][N:34]=2)[CH:31]=1)[CH3:24].[NH4+].[Cl-].C1CCN2C(=NCCC2)CC1>O1CCCC1.CCOC(C)=O.O>[CH3:22][N:23]([CH2:25][C:26]1[CH:27]=[CH:28][C:29]2[N:30]([C:32]([C:35]3[C:36](=[O:37])[NH:38][C:9](=[O:21])[C:10]=3[C:12]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[NH:14][CH:13]=3)=[CH:33][N:34]=2)[CH:31]=1)[CH3:24]

参加物

9

反応物 5

HCID 25517Ammonium ChlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 588944Methyl 3-indoleglyoxylateHCID 23665647Potassium tert-butoxideHCID 59192041HCID 59192041、化合物

生成物 1

HCID 24968236HCID 24968236、化合物収率 44.1%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

Potassium tert-butoxide (1.0 M in THF, 0.55 ml, 0.55 mmol, 2.7 equiv) is added dropwise at room temperature under an atmosphere of argon to a solution of (1H-indol-3-yl)-oxo-acetic acid methyl ester (45 mg, 0.22 mmol, 1.1 equiv) and of 2-(6-dimethylaminomethyl-imidazo[1,2-a]pyridin-3-yl)-acetamide (50 mg, 0.20 mmol) in anhydrous tetrahydrofuran (5.0 ml, dried over molecular sieves). The reaction mixture is stirred for 30 minutes at 0° C. It is then diluted with EtOAc and poured into a saturated aqueous NH4Cl solution. After three extractions with EtOAc, the combined organic layers are dried over Na2SO4, filtered and concentrated in vacuo. The residue is dissolved in N,N-dimethylformamide (5 ml), treated with DBU (0.27 ml, 1.8 mmol, 8.9 equiv) and heated to 110° C. for 10 minutes. After cooling, the reaction mixture is diluted with water and extracted three times with CH2Cl2. The combined organic layers are ished with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification of the residue via preparative HPLC affords the title compound (34 mg, 43%) as its trifluoroacetate salt. 1H NMR (400 MHz, d6-DMSO): δ=12.11 (s, 1H), 11.27 (s, 1H), 9.47 (br s, 1H), 8.21 (d, J=2.9 Hz, 1H), 8.05 (s, 1H), 7.78-7.76 (m, 2H), 7.73 (d, J=8.0 Hz, 1H), 7.29 (dd, J=8.0/4.0 Hz, 1H), 6.94 (t, J=8.0 Hz, 1H), 6.49 (t, J=8.0 Hz, 1H), 5.95 (d, J=8.0 Hz, 1H), 3.48-3.40 (m, 2H), 2.16 (s, 6H). MS (ES+): 386 (M+H)+.

後処理

  1. extractionAfter three extractions with EtOAc
  2. dry with materialthe combined organic layers are dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue is dissolved in N,N-dimethylformamide (5 ml)
  6. temperatureheated to 110° C. for 10 minutes
  7. temperatureAfter cooling
  8. extractionextracted three times with CH2Cl2
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customPurification of the residue via preparative HPLC

出典と根拠

ORDレコード
ord-236082662cdf4e70a2c94287ffa5eb2d
出典データセット
uspto-grants-2012_06
特許番号
US08193236B2

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