6-Aminoquinoline → (R)-2-(5-cyano-6-(quinolin-6-ylamino)pyrazin-2-ylamino)-3-(thiophen-2-yl)propanamide

HRID 2200472Notes

Reaction equation

HRID 2200472 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@H:9]([CH2:13][C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)[C:10]([NH2:12])=[O:11])[CH:5]=[N:4][C:3]=1[C:19]#[N:20].[NH2:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[N:28]=[CH:27][CH:26]=[CH:25]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]>[C:19]([C:3]1[N:4]=[CH:5][C:6]([NH:8][C@H:9]([CH2:13][C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)[C:10]([NH2:12])=[O:11])=[N:7][C:2]=1[NH:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[N:28]=[CH:27][CH:26]=[CH:25]2)#[N:20]

Participants

7

Reactant 4

HCID 113736-AminoquinolineHCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 86685591(R)-2-(6-chloro-5-cyanopyrazin-2-ylamino)-3-(thiophen-2-yl)propanamide

Product 1

HCID 86685592(R)-2-(5-cyano-6-(quinolin-6-ylamino)pyrazin-2-ylamino)-3-(thiophen-2-yl)propanamideYield 32.2%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of (R)-2-(6-chloro-5-cyanopyrazin-2-ylamino)-3-(thiophen-2-yl)propanamide (92 mg, 0.299 mmol), 6-aminoquinoline (60 mg, 0.416 mmol), K2CO3 (80 mg, 0.579 mmol), BINAP (25 mg, 0.040 mmol) and Pd(OAc)2 (15 mg, 0.066 mmol) in dioxane (2 mL) was degassed with Ar, then was stirred at 110 C for 6 h. The mixture was concentrated in vacuo. The residue was purified by HPLC to give (R)-2-(5-cyano-6-(quinolin-6-ylamino)pyrazin-2-ylamino)-3-(thiophen-2-yl)propanamide (40 mg).

Workup

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

Sources & evidence

ORD record
ord-f62779d093df4409b745689fc3a74bba
Source dataset
uspto-grants-2016_06
Patent number
US09359308B2

Reaction notes

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