1-Chloroethyl chloroformate → 2,4,6-trifluoro-N-(6-(piperidine-4-carbonyl)pyridin-2-yl)benzamide

HRID 1667344

反応式

HRID 1667344 の反応式
ClC(OC(Cl)C)=O.[F:8][C:9]1[CH:32]=[C:31]([F:33])[CH:30]=[C:29]([F:34])[C:10]=1[C:11]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([CH:22]2[CH2:27][CH2:26][N:25](C)[CH2:24][CH2:23]2)=[O:21])[N:15]=1)=[O:12]>ClC(Cl)C>[F:34][C:29]1[CH:30]=[C:31]([F:33])[CH:32]=[C:9]([F:8])[C:10]=1[C:11]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([CH:22]2[CH2:23][CH2:24][NH:25][CH2:26][CH2:27]2)=[O:21])[N:15]=1)=[O:12]

参加物

4

反応物 2

HCID 5213051-Chloroethyl chloroformate2 回HCID 11610526Lasmiditan

生成物 1

HCID 179803372,4,6-trifluoro-N-(6-(piperidine-4-carbonyl)pyridin-2-yl)benzamide収率 29.3%

試薬・触媒・溶媒 1

HCID 63651,1-Dichloroethane溶媒

実験手順

Add 1-chloroethyl chloroformate (0.8 g) into a solution of 2,4,6-trifluoro-N-[6-(1-methyl-piperidin-4-ylcarbonyl)-pyridin-2-yl]-benzamide (0.216 g) in dichloroethane (10 mL) and heat at reflux for 1 hr. Then add more 1-chloroethyl chloroformate (1 mL) and heat at reflux overnight. Add methanol (10 mL) to the reaction mixture, concentrate to a small volume, dilute with methanol again, load onto an SCX column (10 g), wash with methanol, and elute with 2M NH3-methanol, evaporate and purify on a silica gel column (CH2Cl2 with 2 M NH3 in methanol) to obtain the title compound (61 mg). Mass spectrum (electric spray) m/z=364 (M+1); 1H NMR (CDCl3): 8.55 (d, J=8.1 Hz, 1H), 7.92 (dd, J=8.0, 8.0 Hz 1H), 7.84 (1H, J=8.0 Hz, 1H), 6.81 (m, 3H), 3.89 (m, 1H), 3.12 (br d, 2H), 2.81 (m, 2H), 1.85 (m, 2H), 1.74 (br, 2H), 1.61 (m, 2H).

後処理

  1. temperatureheat
  2. temperatureat reflux for 1 hr
  3. temperatureheat
  4. temperatureat reflux overnight
  5. concentrationAdd methanol (10 mL) to the reaction mixture, concentrate to a small volume
  6. additiondilute with methanol again
  7. washload onto an SCX column (10 g), wash with methanol
  8. washelute with 2M NH3-methanol
  9. customevaporate
  10. custompurify on a silica gel column (CH2Cl2 with 2 M NH3 in methanol)

出典と根拠

ORDレコード
ord-877bebfcc2904c76b2c4cb6a962bdb4c
出典データセット
uspto-grants-2011_10
特許番号
US08044207B2

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