Diisopropylethylamine → 1h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,1-[(4-fluorophenyl)methyl]-3-[(3-oxo-1-piperazinyl)methyl]-,methyl ester

HRID 2377106ノート

反応式

HRID 2377106 の反応式
F[C:2]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:3]=1[CH2:4][N:5]1[C:9]2=[CH:10][N:11]=[C:12]([C:14]([O:16][CH3:17])=[O:15])[CH:13]=[C:8]2[C:7]([CH2:18]SC2C=CC=CC=2)=[CH:6]1.[NH:31]1[CH2:36][CH2:35][NH:34][CH2:33][C:32]1=[O:37].CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+]>CN(C=O)C>[F:30][C:28]1[CH:29]=[CH:2][C:3]([CH2:4][N:5]2[C:9]3=[CH:10][N:11]=[C:12]([C:14]([O:16][CH3:17])=[O:15])[CH:13]=[C:8]3[C:7]([CH2:18][N:34]3[CH2:35][CH2:36][NH:31][C:32](=[O:37])[CH2:33]3)=[CH:6]2)=[CH:26][CH:27]=1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 231360Piperazin-2-oneHCID 516892Sodium BicarbonateHCID 691988651h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,1-[(2,4-difluorophenyl)methyl]-3-[(phenylthio)methyl]-,methyl ester

生成物 1

HCID 598558121h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,1-[(4-fluorophenyl)methyl]-3-[(3-oxo-1-piperazinyl)methyl]-,methyl ester収率 95.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
50 °C

実験手順

A solution of methyl 3-(chloromethyl)-1-(4-fluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate (24 mL, 2.0M in CH2Cl2, 48.3 mmol) [prepared as described in step 2 of example 40] was evaporated in vacuo to a residue. To this residue, anhydrous DMF (150 mL) and piperazin-2-one (386.4 mmol, 38.689, 8.0 eq.) were added followed by i-Pr2NEt (18.77 g, 145.2 mmol, 25.29 mL, 3 eq.). The mixture, under nitrogen, was placed in an oil bath and the bath was warmed to 50° C. After stirring for 4 hours (50° C.) the reaction was judged to be complete by HPLC-MS analysis. The volatiles were removed in vacuo (ca. 2 torr, at 60° C.) to give a yellow residue. Saturated aqueous sodium bicarbonate (300 mL) was added. White solid precipitated out, and the mixture was sonicated for 30 min and cooled to 10° C. The solid was filtered, washed with cold water (50 mL), and dried in vacuo to afford 18.2 g (95%) of methyl 1-(4-fluorobenzyl)-3-((3-oxopiperazin-1-yl)methyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate. LC-MS (Eclipse XDB-C8, 0.8 mL/min, gradient 80:20 to 5:95H2O (+0.1% HOAc):CH3CN—5 minutes, APCI, +mode): RT—1.41 min, m/e=397.20 (M+H+, base). 1H NMR (300 MHz, DMSO-D6) d ppm 2.55 (t, 2H) 2.92 (s, 2H) 3.11 (s, 2H) 3.74 (s, 2H) 3.84 (s, 3H) 5.56 (s, 2H) 7.16 (t, J=8.85 Hz, 2H) 7.34 (dd, J=8.19, 5.75 Hz, 2H) 7.71 (s, 1H) 7.81 (s, 1H) 8.41 (s, 1H) 8.93 (s, 1H).

後処理

  1. customThe mixture, under nitrogen, was placed in an oil bath
  2. customThe volatiles were removed in vacuo (ca. 2 torr, at 60° C.)
  3. customto give a yellow residue
  4. customWhite solid precipitated out
  5. customthe mixture was sonicated for 30 min
  6. temperaturecooled to 10° C
  7. filtrationThe solid was filtered
  8. washwashed with cold water (50 mL)
  9. customdried in vacuo

出典と根拠

ORDレコード
ord-1a69b6ca792c4a1ab8642230c6f6fb2e
出典データセット
uspto-grants-2008_12
特許番号
US07468375B2

反応ノート

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