Sodium Carbonate → 2-[4-Amino-5-(2-benzyl-2H-indazol-6-yl)-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl]-cyclopropanecarboxylic acid ethyl ester

HRID 1972877ノート

反応式

HRID 1972877 の反応式
[CH2:1]([O:3][C:4]([CH:6]1[CH2:8][CH:7]1[CH2:9][C:10]1[N:18]2[C:13]([C:14]([NH2:19])=[N:15][CH:16]=[N:17]2)=[C:12](Br)[CH:11]=1)=[O:5])[CH3:2].[CH2:21]([N:28]1[CH:36]=[C:35]2[C:30]([CH:31]=[C:32](B3OC(C)(C)C(C)(C)O3)[CH:33]=[CH:34]2)=[N:29]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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>[CH2:1]([O:3][C:4]([CH:6]1[CH2:8][CH:7]1[CH2:9][C:10]1[N:18]2[C:13]([C:14]([NH2:19])=[N:15][CH:16]=[N:17]2)=[C:12]([C:32]2[CH:33]=[CH:34][C:35]3[C:30]([CH:31]=2)=[N:29][N:28]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:36]=3)[CH:11]=1)=[O:5])[CH3:2]

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 585293132-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-IndazoleHCID 585297512-(4-Amino-5-bromo-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl)-cyclopropanecarboxylic acid ethyl ester

生成物 1

HCID 585293712-[4-Amino-5-(2-benzyl-2H-indazol-6-yl)-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl]-cyclopropanecarboxylic acid ethyl ester収率 54%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 2-(4-amino-5-bromo-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl)-cyclopropanecarboxylic acid ethyl ester (1.33 g, 4 mmol) in degassed DMF (6.6 mL) was added 2-benzyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2H-indazole (2.1 g, 6.3 mmol), Pd(PPh3)4, and 2N Na2CO3 solution (5.3 mL). The reaction was irradiated in a microwave reactor at 150° C. for 10 min. After cooling the mixture was partitioned between EtOAc and H2O. The organic phase was separated and dried over Na2SO4, filtered, and evaporated in vacuo. The crude was purified by Biotage® (50-100% EtOAc/hexane) to give the title product as an off white solid, 1.0 g (yield 54%). 1H NMR (300 MHz, DMSO-d6) δ 8.60 (s, 1 H), 8.05 (d, 2 H), 8.0 (s, 1 H), 7.90 (d, 1 H), 7.70 (s, 1 H), 7.60-7.40 (m, 7 H), 7.25 (d, 1 H), 7.20 (s, 1 H), 5.70 (s, 2 H), 4.0 (m, 2 H), 3.0 (m, 2 H), 1.70 (m, 2 H), 1.2-1.0 (m, 5 H); ES-MS m/z 5467.27 [M+H]+, HPLC RT (min) 2.79.

後処理

  1. customThe reaction was irradiated in a microwave reactor at 150° C. for 10 min
  2. temperatureAfter cooling the mixture
  3. customwas partitioned between EtOAc and H2O
  4. customThe organic phase was separated
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe crude was purified by Biotage® (50-100% EtOAc/hexane)

出典と根拠

ORDレコード
ord-bd3aac42f33446979aeb8df1d6f1e355
出典データセット
uspto-grants-2013_04
特許番号
US08431695B2

反応ノート

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