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

HRID 82068ノート

反応式

HRID 82068 の反応式
[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]

参加物

7

反応物 4

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

生成物 1

HCID 401425785-bromo-N-(cyclopropylmethyl)nicotinamide収率 71.1%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of 5-bromonicotinic acid (XXVIII) (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 (XXIX) 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).

後処理

  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

出典と根拠

ORDレコード
ord-520a6d30d8a846eb9db19857bc0db42c
出典データセット
uspto-grants-2014_09
特許番号
US08846714B2

反応ノート

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