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Potassium Carbonate → 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(4-(pyridin-4-yl)phenylamino)pyrazine-2-carbonitrile

HRID 2200453
ノート
印刷プレビュー

反応式

HRID 2200453 の反応式
[NH2:1][C@H:2]1[C:7]([F:9])([F:8])[CH2:6][CH2:5][CH2:4][C@H:3]1[NH:10][C:11]1[N:12]=[C:13](Cl)[C:14]([C:17]#[N:18])=[N:15][CH:16]=1.[N:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=2)=[CH:22][CH:21]=1.C([O-])([O-])=O.[K+].[K+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:1][C@H:2]1[C:7]([F:9])([F:8])[CH2:6][CH2:5][CH2:4][C@H:3]1[NH:10][C:11]1[N:12]=[C:13]([NH:30][C:29]2[CH:28]=[CH:27][C:26]([C:23]3[CH:22]=[CH:21][N:20]=[CH:25][CH:24]=3)=[CH:32][CH:31]=2)[C:14]([C:17]#[N:18])=[N:15][CH:16]=1
参加物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 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 15126544-(Pyridin-4-yl)anilineHCID 866855565-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-chloropyrazine-2-carbonitrile

生成物 1

HCID 866855795-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(4-(pyridin-4-yl)phenylamino)pyrazine-2-carbonitrile収率 37.9%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

実験手順

A mixture of 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-chloropyrazine-2-carbonitrile (74 mg, 0.257 mmol), 4-(pyridin-4-yl)aniline (60 mg, 0.352 mmol), K2CO3 (100 mg, 0.724 mmol), BINAP (25 mg, 0.040 mmol) and Pd(OAc)2 (15 mg, 0.066 mmol) in dioxane (4 mL) was degassed with Ar, then was stirred at 110 C for 20 h. The mixture was concentrated in vacuo. The residue was purified by HPLC to give 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(4-(pyridin-4-yl)phenylamino)pyrazine-2-carbonitrile (41 mg). The compound 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(4-(pyridin-4-yl)phenylamino)pyrazine-2-carbonitrile (41 mg, 0.097 mmol) was dissolved in EtOH (2 mL) and DMSO (1 mL), aq. 1N NaOH (1.0 mL) and aq. H2O2 (30%, 1.0 mL) were added. The mixture was stirred at room temperature for 15 min. HOAc (0.1 mL) was added. The mixture was then concentrated in vacuo. The residue was purified by HPLC to give the titled compound (32 mg). MS 440.3 (M+H); UV 201.7, 242.5, 278.7 nm; t 0.384 min.

後処理

  1. customwas degassed with Ar
  2. concentrationThe mixture was concentrated in vacuo
  3. customThe residue was purified by HPLC

出典と根拠

ORDレコード
ord-68efa8a360aa47a29d3bea1cd01b84f8
出典データセット
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09359308B2

反応ノート

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