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

HRID 242918

反応式

HRID 242918 の反応式
[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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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

後処理

  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)

出典と根拠

ORDレコード
ord-c126b6359c714b53b2d79d8abfd651ad
出典データセット
uspto-grants-2014_02
特許番号
US08653089B2

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