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Nitrogen → (2S)-Methyl 2-(7-(4-allylchroman-6-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 1400712
ノート
印刷プレビュー

反応式

HRID 1400712 の反応式
[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:28]=[C:11]3[N:12]=[C:13]([CH3:27])[C:14]([C@H:17]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C:18]([O:20][CH3:21])=[O:19])=[C:15](I)[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:29]([CH:32]1[C:41]2[C:36](=[CH:37][CH:38]=[C:39](B3OC(C)(C)C(C)(C)O3)[CH:40]=2)[O:35][CH2:34][CH2:33]1)[CH:30]=[CH2:31].C([O-])([O-])=O.[Na+].[Na+].N#N>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>[CH2:29]([CH:32]1[C:41]2[C:36](=[CH:37][CH:38]=[C:39]([C:15]3[N:10]4[N:9]=[C:8]([C:4]5[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=5)[CH:28]=[C:11]4[N:12]=[C:13]([CH3:27])[C:14]=3[C@H:17]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C:18]([O:20][CH3:21])=[O:19])[CH:40]=2)[O:35][CH2:34][CH2:33]1)[CH:30]=[CH2:31]
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 947NitrogenHCID 10340Sodium CarbonateHCID 86710746(S)-methyl 2-(2-(3-bromophenyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateHCID 867107632-(4-Allylchroman-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

生成物 1

HCID 86710765(2S)-Methyl 2-(7-(4-allylchroman-6-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate
収率 190.6%

試薬・触媒・溶媒 2

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

反応条件

温度
90 °C

実験手順

A solution of (S)-methyl 2-(2-(3-bromophenyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.375 g, 0.374 mmol), 2-(4-allylchroman-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.123 g, 0.411 mmol) and 2.0 M Na2CO3 (0.374 ml, 0.747 mmol) in DMF (3.74 ml) was sparged with N2 for 10 min, treated with Pd(Ph3P)4 (0.030 g, 0.026 mmol), sparged for 5 minutes, then heated (90° C.) for 16 h. The reaction was cooled, diluted with water (20 mL) and extracted with EtOAc. The organic layer was dried (MgSO4), filtered, and concentrated and the residue was purified by biotage (40 g SiO2, 0% (3 CV), 0-40% (15 CV), 60% (2 CV), EtOAc in hexanes). Fractions containing desired product combined, concentrated and re-purified (40 g SiO2, 0% (3 CV), 0-60% (15 CV), 60% (2 CV), EtOAc in hexanes) to afford the desired product (0.431 g, 0.713 mmol, 44.6% yield). LCMS (M+H)=606.4.

後処理

  1. customsparged for 5 minutes
  2. temperatureThe reaction was cooled
  3. additiondiluted with water (20 mL)
  4. extractionextracted with EtOAc
  5. dry with materialThe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthe residue was purified by biotage (40 g SiO2, 0% (3 CV), 0-40% (15 CV), 60% (2 CV), EtOAc in hexanes)
  9. additionFractions containing desired product
  10. concentrationconcentrated
  11. customre-purified (40 g SiO2, 0% (3 CV), 0-60% (15 CV), 60% (2 CV), EtOAc in hexanes)

出典と根拠

ORDレコード
ord-2ca9e898352e4897a18360a891527b1e
出典データセット
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08906929B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート