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

HRID 62088ノート

反応式

HRID 62088 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-39d8250a3def4c9494e944f64dc1d233
出典データセット
uspto-grants-2016_09
特許番号
US09446035B2

反応ノート

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