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Sodium Carbonate → tert-butyl 4-{4-[4-amino-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]phenyl}piperazine-1-carboxylate

HRID 1972768
ノート
印刷プレビュー

反応式

HRID 1972768 の反応式
[NH2:1][C:2]1[C:7]2=[C:8](Br)[CH:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([N:17]4[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[N:6]2[N:5]=[CH:4][N:3]=1.[CH2:31]([N:38]1[CH:46]=[C:45]2[C:40]([CH:41]=[C:42](B3OC(C)(C)C(C)(C)O3)[CH:43]=[CH:44]2)=[N:39]1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[NH2:1][C:2]1[C:7]2=[C:8]([C:42]3[CH:43]=[CH:44][C:45]4[C:40]([CH:41]=3)=[N:39][N:38]([CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH:46]=4)[CH:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([N:17]4[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[N:6]2[N:5]=[CH:4][N:3]=1
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

6

反応物 3

HCID 10340Sodium CarbonateHCID 58529297Tert-butyl 4-[4-(4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)phenyl]piperazine-1-carboxylateHCID 585293132-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-Indazole

生成物 1

HCID 58529864tert-butyl 4-{4-[4-amino-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]phenyl}piperazine-1-carboxylate収率 58%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒
HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

To a stirred solution of tert-butyl 4-[4-(4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)phenyl]piperazine-1-carboxylate (4 mg, 1.25 mmol), 2-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-Indazole (1.04 g, 1.87 mmol), and tetrakis(triphenylphosphine)palladium(0) (144 mg, 0.13 mmol) in degassed DME (5.5 mL) was added aqueous Na2CO3 solution (2 M, 1.87 mL). The reaction was heated (80° C.) for 17 h and then cooled to rt. The mixture was partitioned between ethyl acetate (25 mL) and H2O (25 mL). The layers were separated and the aqueous phase was back extracted with ethyl acetate. The combined organics were washed with brine, dried (Na2SO4), and concentrated to dryness. The crude material was purified by ISCO® chromatography using a gradient of 25 to 75% ethyl acetate in hexanes to afford 378 mg (58%) of the desired product, which contained trace impurities. 1H NMR (300 MHz, DMSO-d6) δ 8.52 (s, 1 H), 7.88 (s, 1 H), 7.78 (d, 1 H), 7.57 (s, 1 H), 7.36-7.31 (m, 5 H), 7.13 (d, 1 H), 6.61 (s, 1 H), 5.64 (s, 2 H), 4.13-3.98 (m, 2 H), 3.35-3.25 (m, 1 H), 2.05-1.96 (m, 2 H), 1.63-1.50 (m, 2 H), 1.41 (s, 9 H); ES-MS m/z 524.2 [M+H]+, HPLC RT (min) 3.08.

後処理

  1. temperaturecooled to rt
  2. customThe mixture was partitioned between ethyl acetate (25 mL) and H2O (25 mL)
  3. customThe layers were separated
  4. extractionthe aqueous phase was back extracted with ethyl acetate
  5. washThe combined organics were washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated to dryness
  8. customThe crude material was purified by ISCO® chromatography

出典と根拠

ORDレコード
ord-650831647ecd4002841aaab8e5648617
出典データセット
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08431695B2

反応ノート

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