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

HRID 332834노트

반응식

HRID 332834 반응식
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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-f26674fd49d24c65b53bc979bd7e47a1
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877760B2

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