Sodium Carbonate → Methyl 5-amino-6-[3-(benzyloxy)-4-chlorophenyl]pyrazine-2-carboxylate

HRID 1040373ノート

反応式

HRID 1040373 の反応式
C1(P(CCCC)C2C=CC=CC=2)C=CC=CC=1.[NH2:18][C:19]1[N:20]=[CH:21][C:22]([C:26]([O:28][CH3:29])=[O:27])=[N:23][C:24]=1Br.[CH2:30]([O:37][C:38]1[CH:39]=[C:40](B(O)O)[CH:41]=[CH:42][C:43]=1[Cl:44])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.O.CCOC(C)=O.[Pd].C(#N)C1C=CC=CC=1.C(#N)C1C=CC=CC=1.C(O)C>[NH2:18][C:19]1[N:20]=[CH:21][C:22]([C:26]([O:28][CH3:29])=[O:27])=[N:23][C:24]=1[C:40]1[CH:41]=[CH:42][C:43]([Cl:44])=[C:38]([O:37][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:39]=1

参加物

9

反応物 4

HCID 10340Sodium CarbonateHCID 80755ButyldiphenylphosphineHCID 23005378(3-(Benzyloxy)-4-chlorophenyl)boronic acidHCID 29983315Methyl 5-amino-6-bromopyrazine-2-carboxylate

生成物 1

HCID 66721267Methyl 5-amino-6-[3-(benzyloxy)-4-chlorophenyl]pyrazine-2-carboxylate収率 50.3%

試薬・触媒・溶媒 4

HCID 86637365(Bis-benzonitrile)-palladium触媒HCID 702Ethanol溶媒HCID 1140Toluene溶媒HCID 22728543Water ethylacetate溶媒

実験手順

Stir a suspension of 137 mg (0.36 mmol) of (bis-benzonitrile)-palladium II dichloride and 183 mg (0.43 mmol) of diphenylphosphinobutane in 7 mL of toluene under argon for 30 min at room temperature. Then add, while bubbling with argon, 1.66 g (7.15 mmol) of methyl 5-amino-6-bromopyrazine-2-carboxylate, 1.97 g (7.51 mmol) of [3-(benzyloxy)-4-chlorophenyl]boronic acid, 2.4 mL of ethanol and 3.58 mL (7.15 mmol) of a 2N aqueous solution of sodium carbonate. Reflux the reaction mixture for 5 h 30 min and then distribute in 100 mL of a water/EtOAc 1:1 mixture. Wash the organic phase with 50 mL of water, dry over Na2SO4 and concentrate under reduced pressure. Purify the residue obtained by silica gel column chromatography, eluting with a cyclohexane/EtOAc gradient from 50 to 100% of EtOAc. After concentration under reduced pressure, we obtain 1.33 g of methyl 5-amino-6-[3-(benzyloxy)-4-chlorophenyl]pyrazine-2-carboxylate in the form of yellow wax.

後処理

  1. additionThen add
  2. temperatureReflux the reaction mixture for 5 h 30 min
  3. washWash the organic phase with 50 mL of water
  4. dry with materialdry over Na2SO4
  5. concentrationconcentrate under reduced pressure
  6. customPurify the residue
  7. customobtained by silica gel column chromatography
  8. washeluting with a cyclohexane/EtOAc gradient from 50 to 100% of EtOAc
  9. concentrationAfter concentration under reduced pressure, we

出典と根拠

ORDレコード
ord-fd77a90a30384fecad8b42b43765f64e
出典データセット
uspto-grants-2013_10
特許番号
US08552201B2

反応ノート

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