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Dimethylformamide → 6-[(4-{3-cyano-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}piperazin-1-yl)carbonyl]-5-fluoronicotinonitrile

HRID 1772798
ノート
印刷プレビュー

反応式

HRID 1772798 の反応式
Cl[C:2]1[CH:3]=[C:4]([F:35])[C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH:17]([N:21]3[CH:25]=[C:24]([C:26]4[C:27]5[CH:34]=[CH:33][NH:32][C:28]=5[N:29]=[CH:30][N:31]=4)[CH:23]=[N:22]3)[CH2:18][C:19]#[N:20])[CH2:12][CH2:11]2)=[O:9])=[N:6][CH:7]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[CH3:65][N:66](C=O)C>O.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].[C-]#N.[Zn+2].[C-]#N>[C:19]([CH2:18][CH:17]([N:21]1[CH:25]=[C:24]([C:26]2[C:27]3[CH:34]=[CH:33][NH:32][C:28]=3[N:29]=[CH:30][N:31]=2)[CH:23]=[N:22]1)[CH2:16][N:13]1[CH2:14][CH2:15][N:10]([C:8]([C:5]2[C:4]([F:35])=[CH:3][C:2]([C:65]#[N:66])=[CH:7][N:6]=2)=[O:9])[CH2:11][CH2:12]1)#[N:20]
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 3

HCID 6228DimethylformamideHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 509960004-{4-[(5-chloro-3-fluoropyridin-2-yl)carbonyl]piperazin-1-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile

生成物 1

HCID 509960016-[(4-{3-cyano-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}piperazin-1-yl)carbonyl]-5-fluoronicotinonitrile

試薬・触媒・溶媒 3

HCID 962
Water
触媒
HCID 11186Zinc cyanide (Zn(CN)2)触媒
HCID 9811564Bis(dibenzylideneacetone)palladium触媒

反応条件

温度
150 °C

実験手順

A mixture of 4-{4-[(5-chloro-3-fluoropyridin-2-yl)carbonyl]piperazin-1-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile (15 mg, 0.030 mmol, from Example 1), 2-(Dicyclohexylphosphino)-2′,6′-dimethoxy-1,1′-biphenyl (3.7 mg, 0.0091 mmol), Tris(dibenzylideneacetone)dipalladium(0) (3.3 mg, 0.0036 mmol) and zinc cyanide (18 mg, 0.15 mmol) in DMF (0.50 mL, 6.4 mmol) and one drop of water was degassed by purging with a stream of nitrogen for 5 minutes, then was heated in the microwave for 15 minutes at 150° C. Preparative HPLC-MS, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH, was used to purify the product (6 mg, 40%). 1H NMR (300 MHz, d6-dmso): δ 12.10 (br s, 1H), 8.93 (t, 1H), 8.81 (s, 1H), 8.68 (s, 1H), 8.59 (dd, 1H), 8.37 (s, 1H), 7.60 (d, 1H), 6.97 (d, 1H), 4.98 (tt, 1H), 3.65-3.58 (m, 2H), 3.25-3.19 (m, 2H), 3.19-3.13 (m, 2H), 2.92-2.78 (m, 2H), 2.66-2.25 (m, 4H); LCMS (M+H)+: 485.2.

後処理

  1. customwas degassed
  2. customby purging with a stream of nitrogen for 5 minutes
  3. washPreparative HPLC-MS, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH
  4. customto purify the product (6 mg, 40%)

出典と根拠

ORDレコード
ord-63d362c19db94c958e38f9111e91a6ba
出典データセット
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09249145B2

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