Diisopropylethylamine → 1,1-Dimethylethyl (3R)-3-{[(7-chloro-1,6-naphthyridin-5-yl)amino]methyl}-3-fluoro-1-piperidinecarboxylate

HRID 473318노트

반응식

HRID 473318 반응식
Cl[C:2]1[N:11]=[C:10]([Cl:12])[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.[NH2:13][CH2:14][C@:15]1([F:28])[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16]1.CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[Cl:12][C:10]1[CH:9]=[C:8]2[C:3]([CH:4]=[CH:5][CH:6]=[N:7]2)=[C:2]([NH:13][CH2:14][C@:15]2([F:28])[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:16]2)[N:11]=1

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 122042335,7-Dichloro-1,6-naphthyridineHCID 68210002tert-Butyl (R)-3-(aminomethyl)-3-fluoropiperidine-1-carboxylate

생성물 1

HCID 866768011,1-Dimethylethyl (3R)-3-{[(7-chloro-1,6-naphthyridin-5-yl)amino]methyl}-3-fluoro-1-piperidinecarboxylate

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
100 °C

실험 절차

To 5,7-dichloro-1,6-naphthyridine (5.01 g, 25.2 mmol) and 1,1-dimethylethyl (3R)-3-(aminomethyl)-3-fluoro-1-piperidinecarboxylate (5.32 g, 22.90 mmol) in NMP (20 ml) was added DIPEA (8.00 ml, 45.8 mmol) and the mixture was stirred at 100° C. for 72 h under nitrogen. The reaction was cooled and partitioned between ethyl acetate and water (200 ml each). The aqueous was washed with ethyl acetate. The combined organics were washed with water and the solvent was removed. The residue was dissolved in DCM and loaded onto a 100 g silica SNAP column and purified on the SP4 eluting with 0-50% ethyl acetate in cyclohexane over 17 CVs. Appropriate fractions were combined and the solvent was removed to give the title compound as a pale orange solid which was dried under high vacuum for 2 h (7.61 g).

후처리

  1. temperatureThe reaction was cooled
  2. custompartitioned between ethyl acetate and water (200 ml each)
  3. washThe aqueous was washed with ethyl acetate
  4. washThe combined organics were washed with water
  5. customthe solvent was removed
  6. dissolutionThe residue was dissolved in DCM
  7. custompurified on the SP4
  8. washeluting with 0-50% ethyl acetate in cyclohexane over 17 CVs
  9. customthe solvent was removed

출처 및 근거

ORD 기록
ord-26504d44e3254af3a4a85fe74888d429
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08633319B2

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