Triethylamine → (R)-Methyl 6-(1-amino-4-methyl-1-oxopentan-2-ylamino)-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinate

HRID 711485Notes

Reaction equation

HRID 711485 reaction equation
Cl[C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([S:21]([CH3:24])(=[O:23])=[O:22])[CH:16]=2)[N:3]=1.[NH2:25][C@H:26]([CH2:30][CH:31]([CH3:33])[CH3:32])[C:27]([NH2:29])=[O:28].CCN(CC)CC.C([O-])(O)=O.[Na+]>CN(C=O)C>[NH2:29][C:27](=[O:28])[C@H:26]([NH:25][C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([S:21]([CH3:24])(=[O:23])=[O:22])[CH:16]=2)[N:3]=1)[CH2:30][CH:31]([CH3:33])[CH3:32]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 7271815(R)-2-Amino-4-methylpentanamideHCID 58317716Methyl 6-chloro-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinate

Product 1

HCID 67239420(R)-Methyl 6-(1-amino-4-methyl-1-oxopentan-2-ylamino)-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinateYield 50.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of methyl 6-chloro-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinate (120.7 mg, 0.330 mmol), (R)-2-amino-4-methylpentanamide (67.1 mg, 0.515 mmol), and Et3N (0.1 mL, 0.717 mmol) in DMF (4 mL) was stirred at 60° C. for 14 h. Saturated aq NaHCO3 (20 mL) was added to the mixture, which was subsequently extracted with EtOAc (2×30 mL). The organic layers were washed with saturated aq NaHCO3 (20 mL), water (20 mL) and brine (20 mL), were dried over anhydrous Na2SO4, and filtered (DM1020). The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (SiO2, hexanes/EtOAc=1/2) and then triturated with IPE to give the title compound (76 mg, 50%).

Workup

  1. extractionwas subsequently extracted with EtOAc (2×30 mL)
  2. washThe organic layers were washed with saturated aq NaHCO3 (20 mL), water (20 mL) and brine (20 mL)
  3. dry with materialwere dried over anhydrous Na2SO4
  4. filtrationfiltered (DM1020)
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by column chromatography (SiO2, hexanes/EtOAc=1/2)
  7. customtriturated with IPE

Sources & evidence

ORD record
ord-06eba0f405a64128bc61515d38881a2b
Source dataset
uspto-grants-2015_11
Patent number
US09181255B2

Reaction notes

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