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

HRID 332834Notes

Reaction equation

HRID 332834 reaction equation
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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-f26674fd49d24c65b53bc979bd7e47a1
Source dataset
uspto-grants-2014_11
Patent number
US08877760B2

Reaction notes

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