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

HRID 516021노트

반응식

HRID 516021 반응식
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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
60 °C

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-34132de5c7ab469aa455ab8889860309
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108970B2

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