6-Chloronicotinic acid → 4-[(6-Chloro-pyridine-3-carbonyl)-amino]-4-cyano-piperidine-1-carboxylic acid tert-butyl ester

HRID 913337노트

반응식

HRID 913337 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([NH2:16])([C:14]#[N:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[Cl:44][C:45]1[CH:53]=[CH:52][C:48]([C:49](O)=[O:50])=[CH:47][N:46]=1>C1COCC1.C(N(C(C)C)C(C)C)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]([NH:16][C:49]([C:48]2[CH:47]=[N:46][C:45]([Cl:44])=[CH:53][CH:52]=2)=[O:50])([C:14]#[N:15])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

참가 물질

6

반응물 3

HCID 792226-Chloronicotinic acidHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 22091429tert-Butyl 4-amino-4-cyanopiperidine-1-carboxylate

생성물 1

HCID 866250164-[(6-Chloro-pyridine-3-carbonyl)-amino]-4-cyano-piperidine-1-carboxylic acid tert-butyl ester수율 74%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 81531Diisopropylethylamine용매

실험 절차

To a solution of 4-amino-4-cyano-piperidine-1-carboxylic acid tert-butyl ester (0.527 g, 2.34 mmol, 1.0 equiv; prepared as described in WO 03/104 236 A1 (Bristol-Myers Squibb Company); [CAS RN 331281-25-5]) in anhydrous THF (12 mL) and N-ethyl diisopropylamine (0.48 mL) was added in the presence of (benzotriazol-1-yloxy)-tris-(dimethylamino)phosphonium hexafluorophosphate (1.138 g, 2.58 mmol, 1.1 equiv; BOP reagent) 6-chloro-nicotinic acid (0.369 g, 2.34 mmol, 1.0 equiv) and the reaction mixture stirred at rt for 12 h. The reaction mixture was poured on crashed ice/NH4Cl, extracted with ethyl acetate (2×200 mL) and the combined organic phases washed with a sat. solution of NaCl (2×100 mL) and water (2×100 mL). The organic phase was dried over Na2SO4, concentrated by evaporation under reduced pressure and the crude material purified by silica column chromatography eluting with a mixture of ethyl acetate/triethylamine (97:3) providing 0.63 g (74%) of the title compound as off-white solid. MS (ISP): 365.1 [M+H]+

후처리

  1. additionThe reaction mixture was poured
  2. extractionextracted with ethyl acetate (2×200 mL)
  3. washthe combined organic phases washed with a sat. solution of NaCl (2×100 mL) and water (2×100 mL)
  4. dry with materialThe organic phase was dried over Na2SO4
  5. concentrationconcentrated by evaporation under reduced pressure
  6. customthe crude material purified by silica column chromatography
  7. washeluting with a mixture of ethyl acetate/triethylamine (97:3)

출처 및 근거

ORD 기록
ord-bb85cba21d9044e69a0a732942fb99a8
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08026365B2

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