Cesium carbonate → 5-((1R,2S)-2-aminocyclohexylamino)-3-(isothiazolo[3,4-b]pyridin-3-ylamino)pyrazine-2-carbonitrile

HRID 332834ノート

反応式

HRID 332834 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]2[NH:15]C(=O)OC(C)(C)C)[CH:5]=[N:4][C:3]=1[C:23]#[N:24].[N:25]1[S:26][C:27]([NH2:34])=[C:28]2[CH:33]=[CH:32][CH:31]=[N:30][C:29]=12.C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1>O1CCOCC1.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]>[NH2:15][C@H:10]1[CH2:11][CH2:12][CH2:13][CH2:14][C@H:9]1[NH:8][C:6]1[N:7]=[C:2]([NH:34][C:27]2[S:26][N:25]=[C:29]3[C:28]=2[CH:33]=[CH:32][CH:31]=[N:30]3)[C:3]([C:23]#[N:24])=[N:4][CH:5]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 297118Isothiazolo(3,4-b)pyridin-3-amineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 86685544tert-butyl (1S,2R)-2-(6-chloro-5-cyanopyrazin-2-ylamino)cyclohexylcarbamate

生成物 1

HCID 866856225-((1R,2S)-2-aminocyclohexylamino)-3-(isothiazolo[3,4-b]pyridin-3-ylamino)pyrazine-2-carbonitrile収率 65.5%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

実験手順

A mixture of tert-butyl (1S,2R)-2-(6-chloro-5-cyanopyrazin-2-ylamino)cyclohexylcarbamate (53 mg, 0.150 mmol), isothiazolo[3,4-b]pyridin-3-amine (29 mg, 0.0.192 mmol), Cs2CO3 (100 mg, 0.304 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (DavePhos) (12 mg, 0.030 mmol) and Pd2dba3 (15 mg, 0.016 mmol) in dioxane (1 mL) was degassed with Ar, then was stirred at 110 C for 2 h. The mixture was concentrated in vacuo. The residue was dissolved in TFA (4 mL). After 20 min of stirring, excess of TFA was removed in vacuo. The residue was purified by HPLC to give 5-((1R,2S)-2-aminocyclohexylamino)-3-(isothiazolo[3,4-b]pyridin-3-ylamino)pyrazine-2-carbonitrile (36 mg).

後処理

  1. customwas degassed with Ar
  2. concentrationThe mixture was concentrated in vacuo
  3. dissolutionThe residue was dissolved in TFA (4 mL)
  4. stirringAfter 20 min of stirring, excess of TFA
  5. customwas removed in vacuo
  6. customThe residue was purified by HPLC

出典と根拠

ORDレコード
ord-f26674fd49d24c65b53bc979bd7e47a1
出典データセット
uspto-grants-2014_11
特許番号
US08877760B2

反応ノート

読み込み中…