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

HRID 473318ノート

反応式

HRID 473318 の反応式
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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
100 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-26504d44e3254af3a4a85fe74888d429
出典データセット
uspto-grants-2014_01
特許番号
US08633319B2

反応ノート

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