Sodium Bicarbonate → {3-[4-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl}methanol

HRID 28908

反応式

HRID 28908 の反応式
[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([S:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:9](I)=[CH:10][C:3]=12.[OH:21][CH2:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1.C([O-])(O)=O.[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([S:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:9]([C:27]3[CH:28]=[C:23]([CH2:22][OH:21])[CH:24]=[CH:25][CH:26]=3)=[CH:10][C:3]=12

参加物

6

反応物 3

HCID 516892Sodium BicarbonateHCID 2734662[3-(Hydroxymethyl)phenyl]boronic acidHCID 469079554-Bromo-2-iodo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine2 回

生成物 1

HCID 58980081{3-[4-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl}methanol収率 66%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 312751,4-Dioxane溶媒

実験手順

The above reaction was repeated two more times with 4-bromo-2-iodo-1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridine (15 g of a reported 90% pure lot from CiVenti, 29.1 mMol) and 3-(hydroxymethyl)benzeneboronic acid (4.0 g, 26.3 mMol the first time, then 3.7 g, 24.3 mMol the second time). In both reactions dioxane (300 mL), aq. sat. NaHCO3 (75 mL), and (1.0 g, 0.86 mMol) of Pd(PPh3)4 was used. The amount of a bis-coupled side product was reduced from 26% to 15% and 13% respectively (by LCMS) in each of the reactions. All three reaction products (derived from a total of 40 g of 4-bromo-2-iodo-1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridine, 90% pure lot from CiVenti=36 g, 77.7 mMol) were combined and purified by flash chromatography by silica gel (10 to 15% EtOAc/CH2Cl2) to give the title compound (22.77 g, 66%) as a white solid: MS (ES) m/e 443.2 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ 8.27 (d, J=5.1 Hz, 1H), 7.85-7.91 (m, 2H), 7.70 (t, J=7.5 Hz, 1H), 7.63 (d, J=5.3 Hz, 1H), 7.59 (app. t, J=7.8 Hz, 2H), 7.53 (s, 1H), 7.44-7.50 (m, 3H), 6.75 (s, 1H), 5.35 (t, J=5.8 Hz, 1H), 4.62 (d, J=5.8 Hz, 2H).

後処理

  1. customThe above reaction
  2. customAll three reaction products (
  3. custompurified by flash chromatography by silica gel (10 to 15% EtOAc/CH2Cl2)

出典と根拠

ORDレコード
ord-c542f1afe1564f7ab07cca20bf30d238
出典データセット
uspto-grants-2008_09
特許番号
US07419988B2

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