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4-Bromopyridinium chloride → 2-[1-[(4-ethoxy-2,6-difluorophenyl)methyl]-5,6-dihydro-4H-cyclopenta[c]pyrazol-3-yl]-5-methoxy-N-pyridin-4-ylpyrimidin-4-amine

HRID 1482930
ノート
印刷プレビュー

反応式

HRID 1482930 の反応式
[CH2:1]([O:3][C:4]1[CH:27]=[C:26]([F:28])[C:7]([CH2:8][N:9]2[C:13]3[CH2:14][CH2:15][CH2:16][C:12]=3[C:11]([C:17]3[N:22]=[C:21]([NH2:23])[C:20]([O:24][CH3:25])=[CH:19][N:18]=3)=[N:10]2)=[C:6]([F:29])[CH:5]=1)[CH3:2].Cl.Br[C:32]1[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([F:29])[C:7]([CH2:8][N:9]2[C:13]3[CH2:14][CH2:15][CH2:16][C:12]=3[C:11]([C:17]3[N:22]=[C:21]([NH:23][C:32]4[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=4)[C:20]([O:24][CH3:25])=[CH:19][N:18]=3)=[N:10]2)=[C:26]([F:28])[CH:27]=1)[CH3:2]
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 881004-Bromopyridinium chlorideHCID 634876Binap, (A+-)-HCID 900126782-[1-(4-Ethoxy-2,6-difluorobenzyl)-1,4,5,6-tetrahydrocyclopenta-[c]pyrazol-3-yl]-5-methoxypyrimidin-4-amine

生成物 1

HCID 722022542-[1-[(4-ethoxy-2,6-difluorophenyl)methyl]-5,6-dihydro-4H-cyclopenta[c]pyrazol-3-yl]-5-methoxy-N-pyridin-4-ylpyrimidin-4-amine

試薬・触媒・溶媒 2

HCID 9811564
Bis(dibenzylideneacetone)palladium
触媒
HCID 6228Dimethylformamide溶媒

反応条件

温度
100 °C

実験手順

1.74 g of 2-[1-(4-ethoxy-2,6-difluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]-pyrazol-3-yl]-5-methoxypyrimidin-4-amine 1-4-1 (4.34 mmol, 1.00 eq.), 1.26 g of 4-bromopyridine hydrochloride (1:1) (6.50 mmol, 1.50 eq.), 540 mg of (R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaphtyl (0.867 mmol, 0.20 eq.), 1.66 g of sodium-tert-buylat (17.3 mmol, 4.00 eq.) and 198 mg of tris(dibenzylideneacetone)dipalladium(0) (0.867 mmol, 0.20 eq.) were suspended in 23 mL of dry DMF and stirred under nitrogen atmosphere at 100° C. bath temperature for 24 h. The reaction mixture was partitioned between half saturated aqueous ammonium chloride solution and DCM/isopropanol (4:1). The separated aqueous layer was extracted twice with DCM/isopropanol (4:1). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. Toluene was added and concentrated in vacuo. The residue was purified by flash chromatography (hexane (50-100%)/ethyl acetate and ethyl acetate (0-100%)/methanole): 655 mg (1.29 mmol, 30%) of analytically pure target compound.

後処理

  1. customThe reaction mixture was partitioned between half saturated aqueous ammonium chloride solution and DCM/isopropanol (4:1)
  2. extractionThe separated aqueous layer was extracted twice with DCM/isopropanol (4:1)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. additionToluene was added
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography (hexane (50-100%)/ethyl acetate and ethyl acetate (0-100%)/methanole)

出典と根拠

ORDレコード
ord-23e445e46a0144aa8b06b48c163eb9f4
出典データセット
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09416125B2

反応ノート

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