6-Aminoquinoline → 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(quinolin-6-ylamino)pyrazine-2-carbonitrile

HRID 332752Notes

Reaction equation

HRID 332752 reaction equation
[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.[NH2:20][C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[N:27]=[CH:26][CH:25]=[CH:24]2.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:20][C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[N:27]=[CH:26][CH:25]=[CH:24]3)[C:14]([C:17]#[N:18])=[N:15][CH:16]=1

Participants

7

Reactant 4

HCID 113736-AminoquinolineHCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 866855565-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-chloropyrazine-2-carbonitrile

Product 1

HCID 866855595-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(quinolin-6-ylamino)pyrazine-2-carbonitrile

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-chloropyrazine-2-carbonitrile (97 mg, 0.241 mmol), 6-aminoquinoline (50 mg, 0.347 mmol), K2CO3 (100 mg, 0.724 mmol), BINAP (25 mg, 0.040 mmol) and Pd(OAc)2 (10 mg, 0.044 mmol) in dioxane (2 mL) was degassed with Ar, then was stirred at 110 C for 20 h. Water was added to induce precipitation. The precipitate was collected, and dried on vacuum to give 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(quinolin-6-ylamino)pyrazine-2-carbonitrile as a solid. The solid 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(quinolin-6-ylamino)pyrazine-2-carbonitrile was dissolved in EtOH (4 mL) and DMSO (2 mL), aq. 1N NaOH (1.0 mL) and aq. H2O2 (50%, 1.0 mL) were added. The mixture was stirred at room temperature for 30 min. HOAc (0.5 mL) was added. The mixture was then concentrated in vacuo. The residue was purified by HPLC to give the titled compound (26 mg). MS 414.2 (M+H); UV 200.0, 263.4, 296.0, 356.1 nm; t 0.335 min.

Workup

  1. customwas degassed with Ar
  2. additionWater was added
  3. customprecipitation
  4. customThe precipitate was collected
  5. customdried on vacuum

Sources & evidence

ORD record
ord-4a9c58a850524f838d99a8c21a89de1a
Source dataset
uspto-grants-2014_11
Patent number
US08877760B2

Reaction notes

Loading…