Potassium Carbonate → Tert-butyl 4-(6-(2-amino-5-bromonicotinoyl)pyridin-2-yl)-1,4-diazepane-1-carboxylate

HRID 1929360

반응식

HRID 1929360 반응식
[NH2:1][C:2]1[C:7]([C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12](Br)[N:11]=2)=[O:9])=[CH:6][C:5]([Br:17])=[CH:4][N:3]=1.[C:18]([N:25]1[CH2:31][CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([Br:17])=[CH:6][C:7]=1[C:8]([C:10]1[N:11]=[C:12]([N:28]2[CH2:29][CH2:30][CH2:31][N:25]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:26][CH2:27]2)[CH:13]=[CH:14][CH:15]=1)=[O:9]

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 2756058Tert-butyl 1,4-diazepane-1-carboxylate2회HCID 57690616(2-Amino-5-bromopyridin-3-yl)(6-bromopyridin-2-yl)methanone

생성물 1

HCID 57690601Tert-butyl 4-(6-(2-amino-5-bromonicotinoyl)pyridin-2-yl)-1,4-diazepane-1-carboxylate수율 37%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
95 °C

실험 절차

A mixture of (2-amino-5-bromopyridin-3-yl)(6-bromopyridin-2-yl)methanone (6.0 g, 16.8 mmol), 1-Boc-homopiperazine (3.64 ml, 18.48 mmol) and K2CO3 (8.13 g, 58.8 mmol) in DMF (50 ml) was heated at 95° C. for 17 hours. Additional 1-Boc-homopiperazine (0.3 ml, 0.1 eq) was added and the mixture heated at 95° C. for a further 4 hours for reaction to go to completion. Reaction mixture was then allowed to cool to room temperature and solvent removed in vacuo. The resulting solid was slurried in EtOAc and filtered through a short pad of silica, washing through with EtOAc and the resulting filtrate was then concentrated to dryness in vacuo. The crude product was purified by flash chromatography on silica (5 to 25% EtOAc/Petrol) to give pure title compound as a yellow solid (2.94 g, 37%). 1H NMR (DMSO-d6) (quoted as a mixture of rotamers) 1.25 (9H, d), 1.91-1.77 (2H, m), 3.34 (2H, masked signal), 3.57-3.50 (2H, m), 3.65-3.62 (2H, m), 3.77-3.70 (2H, m), 6.95 (1H, dd), 7.12 (1H, dd), 7.75-7.69 (1H, m), 7.80 (2H, br s), 8.32 (1H, d), 8.60 (1H, dd). ES+ 477.98.

후처리

  1. temperaturethe mixture heated at 95° C. for a further 4 hours for reaction
  2. customReaction mixture
  3. temperatureto cool to room temperature
  4. customsolvent removed in vacuo
  5. filtrationfiltered through a short pad of silica
  6. washwashing through with EtOAc
  7. concentrationthe resulting filtrate was then concentrated to dryness in vacuo
  8. customThe crude product was purified by flash chromatography on silica (5 to 25% EtOAc/Petrol)

출처 및 근거

ORD 기록
ord-1c860ebbf7324543b3fd3e41219314f6
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188071B2

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