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Sodium Bicarbonate → ethyl 4-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-hydroxy-2-methylbut-3-ynoate

HRID 1398565
ノート
印刷プレビュー

反応式

HRID 1398565 の反応式
I[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH3:18])=[N:7][N:8]2[C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH2:17])[N:12]=2)=[CH:4][CH:3]=1.[OH:19][C:20]([CH3:32])([C:26]#[C:27][Si](C)(C)C)[C:21]([O:23][CH2:24][CH3:25])=[O:22].CCCC[N+](CCCC)(CCCC)CCCC.[F-].C(=O)(O)[O-].[Na+]>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:17][C:13]1[N:12]=[C:11]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([C:27]#[C:26][C:20]([OH:19])([CH3:32])[C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:10]=3)[C:6]([CH3:18])=[N:7]2)[CH:16]=[CH:15][N:14]=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

7

反応物 4

HCID 516892Sodium BicarbonateHCID 2724141Tetrabutylammonium FluorideHCID 681816364-(6-Iodo-3-methylindazol-1-yl)pyrimidin-2-amineHCID 86669592Ethyl 2-hydroxy-2-methyl-4-(trimethylsilyl)but-3-ynoate

生成物 1

HCID 68181861ethyl 4-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-hydroxy-2-methylbut-3-ynoate

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒
HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
50 °C

実験手順

To a solution of 4-(6-iodo-3-methyl-1H-indazol-1-yl)pyrimidin-2-amine (170 mg, 0.38 mmol) in dry THF (3 mL) was introduced bis(triphenylphosphine)palladium(II) chloride (27 mg, 0.04 mmol), ethyl 2-hydroxy-2-methyl-4-(trimethylsilyl)but-3-ynoate (164 mg, 0.76 mmol) and TBAF (0.46 mL of a 1M solution in THF, 0.46 mmol). The solution was warmed to 50° C. for 1.5 hr. After cooling, sodium bicarbonate (4 mL of saturated aqueous NaHCO3) was introduced and the solution extracted with EtOAc (3×10 mL extractions). The combined organic extracts were washed with brine (10 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification by silica gel flash column chromatography (DCM containing a 1-10% gradient of methanol) furnished the title compound as an orange oil: 1H NMR (250 MHz, Chloroform-d) delta 1.39 (3H, t, J=7.1 Hz), 1.83 (3 H, s), 2.60 (3H, s), 4.38 (2H, q, J=7.1 Hz), 5.20 (2H, s), 7.29 (1H, s), 7.34 (1H, dd, J=8.2, 1.3 Hz), 7.60 (1H, dd, J=8.2, 0.7 Hz), 8.29 (1H, d, J=5.7 Hz), 8.83 (1H, s); LC-MS: m/z=+366.05 (M+H)+.

後処理

  1. temperatureAfter cooling
  2. extractionthe solution extracted with EtOAc (3×10 mL extractions)
  3. washThe combined organic extracts were washed with brine (10 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by silica gel flash column chromatography (DCM containing a 1-10% gradient of methanol)

出典と根拠

ORDレコード
ord-040cfa0717a0435cb3202b61b89e3dcc
出典データセット
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08901313B2

反応ノート

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