4-Methylmorpholine → [(S)-1-(4-fluoro-2-phenylaminophenylcarbamoyl)-2-methoxyethyl]carbamic acid tert-butyl ester

HRID 242918

반응식

HRID 242918 반응식
[F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:5]([NH2:8])=[CH:6][CH:7]=1.[C:16]([O:20][C:21]([NH:23][C@@H:24]([CH2:28][O:29][CH3:30])[C:25](O)=[O:26])=[O:22])([CH3:19])([CH3:18])[CH3:17].C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[C:16]([O:20][C:21](=[O:22])[NH:23][C@H:24]([C:25](=[O:26])[NH:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=1[NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH2:28][O:29][CH3:30])([CH3:19])([CH3:17])[CH3:18]

참가 물질

7

반응물 5

HCID 79724-MethylmorpholineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7016354(2S)-2-(((tert-butoxy)carbonyl)amino)-3-methoxypropanoic acidHCID 214506204-Fluoro-2-phenylaminoaniline

생성물 1

HCID 68157542[(S)-1-(4-fluoro-2-phenylaminophenylcarbamoyl)-2-methoxyethyl]carbamic acid tert-butyl ester수율 74%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A mixture of 4-fluoro-N2-phenylbenzene-1,2-diamine (450 mg, 2.2 mmol), (S)-2-tertbutoxycarbonylamino-3-methoxypropionic acid (525 mg, 2.4 mmol), HOAt (330 mg, 2.4 mmol), 4-methylmorpholine (0.53 mL, 4.8 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (460 mg, 2.4 mmol) in DCM (10 mL) was stirred at RT for 18 h. The reaction mixture was partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic phase was washed with brine, dried (MgSO4) concentrated in vacuo and the resulting residue was purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cyclohexane) to afford [(S)-1-(4-fluoro-2-phenylaminophenylcarbamoyl)-2-methoxyethyl]carbamic acid tert-butyl ester (0.655 g, 74%). A solution of the compound thus obtained (0.655 g) in AcOH (10 mL) was heated at 70° C. for 56 h. After cooling to RT, the volatiles were removed in vacuo and the resulting residue partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic layer was washed with brine, dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cyclohexane) to afford the title compound (227 mg, 28%). LCMS (Method J): RT 3.59 and 3.70 min [M+H]+ 386.2

후처리

  1. customThe reaction mixture was partitioned between DCM
  2. washThe organic phase was washed with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customthe resulting residue was purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cyclohexane)

출처 및 근거

ORD 기록
ord-c126b6359c714b53b2d79d8abfd651ad
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08653089B2

연결된 노트

불러오는 중…