Dimethylformamide → 1-[4-amino-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]-2-morpholin-4-ylethanone

HRID 1972821ノート

反応式

HRID 1972821 の反応式
[NH2:1][C:2]1[C:7]2=[C:8](Br)[CH:9]=[C:10]([C:11](=[O:19])[CH2:12][N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[N:6]2[N:5]=[CH:4][N:3]=1.CN(C=O)C.[CH2:26]([N:33]1[CH:41]=[C:40]2[C:35]([CH:36]=[C:37](B3OC(C)(C)C(C)(C)O3)[CH:38]=[CH:39]2)=[N:34]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.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.O>[NH2:1][C:2]1[C:7]2=[C:8]([C:37]3[CH:38]=[CH:39][C:40]4[C:35]([CH:36]=3)=[N:34][N:33]([CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:41]=4)[CH:9]=[C:10]([C:11](=[O:19])[CH2:12][N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[N:6]2[N:5]=[CH:4][N:3]=1

参加物

8

反応物 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 585293132-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-IndazoleHCID 585294241-(4-Amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2-morpholin-4-ylethanone

生成物 1

HCID 585296201-[4-amino-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]-2-morpholin-4-ylethanone収率 16%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a stirred solution of 1-(4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2-morpholin-4-ylethanone (90 mg, 0.27 mmol) and tetrakis(triphenylphosphine)palladium(0) (61 mg, 0.05 mmol), in degassed 1,4-dioxane (1.0 mL) and DMF (2.0 mL) was added 2-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole (97 mg, 0.29 mmol), K2CO3 (80 mg, 0.58 mmol), and H2O (0.3 mL). The mixture was degassed and heated (100° C.) for 17 h and then cooled to rt. The mixture was partitioned between ethyl acetate (25 mL) and saturated aqueous K2CO3 solution (25 mL). The layers were separated and the organic phase was washed, dried (Na2SO4), and concentrated to dryness. The residue was purified by preparative HPLC using a gradient elution from 10% to 70% acetonitrile to obtain 20 mg (16%) of the desired product. 1H-NMR (DMSO-d6) 8.57 (s, 1H), 8.13 (s, 1H), 7.82 (d, 1H), 7.65 (s, 1H), 7.39 (s, 1H), 7.36-7.28 (m, 5H), 7.14 (d, 1H), 5.65 (s, 2H), 3.93 (s, 2H), 3.58-3.56 (m, 4H), 2.56-2.53 (m, 4H); LC-MS [M+H]+=468, RT=2.27 min.

後処理

  1. customThe mixture was degassed
  2. temperaturecooled to rt
  3. customThe mixture was partitioned between ethyl acetate (25 mL) and saturated aqueous K2CO3 solution (25 mL)
  4. customThe layers were separated
  5. washthe organic phase was washed
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated to dryness
  8. customThe residue was purified by preparative HPLC
  9. washa gradient elution from 10% to 70% acetonitrile

出典と根拠

ORDレコード
ord-fdfee513b19a4e6b81336cf7d54959b4
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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