Oxalyl chloride → 5-bromo-N-(cyclopropylmethyl)nicotinamide

HRID 889133노트

반응식

HRID 889133 반응식
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C(Cl)(=O)C(Cl)=O.[CH:17]1([CH2:20][NH2:21])[CH2:19][CH2:18]1.C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([NH:21][CH2:20][CH:17]1[CH2:19][CH2:18]1)=[O:9]

참가 물질

7

반응물 4

HCID 65578Oxalyl chlorideHCID 75646CyclopropanemethanamineHCID 887075-Bromonicotinic acidHCID 516892Sodium Bicarbonate

생성물 1

HCID 401425785-bromo-N-(cyclopropylmethyl)nicotinamide수율 71.1%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

To a solution of 5-bromonicotinic acid (XVI) (1.01 g, 5 mmol) in dry DCM (10 mL) under nitrogen was added oxalyl chloride (0.654 mL, 7.5 mmol) followed by dry DMF (0.1 mL). The solution was stirred at r.t. for 30 min. The solvent was evaporated under vacuum before adding dry pyridine (10 mL) followed by cyclopropylmethanamine (0.39 mL, 4.5 mmol). The solution was stirred at r.t. under nitrogen for 2 h. The solution was poured into ice water, basified with sat. aq. NaHCO3 and extracted with DCM. The combined organic phases were dried over MgSO4, concentrated and dried under vacuum to yield 5-bromo-N-(cyclopropylmethyl)nicotinamide (XVII) as an off-white solid (0.82 g, 3.2 mmol, 71% yield). 1H NMR (DMSO-d6) δ ppm −0.07-0.07 (m, 2H), 0.15-0.29 (m, 2H), 0.68-0.88 (m, 1H), 2.93 (t, J=6.22 Hz, 2H), 8.20 (t, J=1.88 Hz, 1H), 8.62 (d, J=1.70 Hz, 2H), 8.75 (s, 1H); ESIMS found C10H11BrN2O m/z 254, 256 (M+, M+2).

후처리

  1. customThe solvent was evaporated under vacuum
  2. additionbefore adding dry pyridine (10 mL)
  3. stirringThe solution was stirred at r.t. under nitrogen for 2 h
  4. extractionextracted with DCM
  5. dry with materialThe combined organic phases were dried over MgSO4
  6. concentrationconcentrated
  7. customdried under vacuum

출처 및 근거

ORD 기록
ord-1dafb740cb2d471fb262c9228bd35e3d
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08252812B2

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