Lithium Chloride → 2-Amino-5-pyrazin-2-yl-4-trifluoromethyl-benzoic acid methyl ester

HRID 1441646

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HRID 1441646 반응식
[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8](I)[C:7]([C:11]([F:14])([F:13])[F:12])=[CH:6][C:5]=1[NH2:15].C([Sn](CCCC)(CCCC)[C:22]1[CH:27]=[N:26][CH:25]=[CH:24][N:23]=1)CCC.[Li+].[Cl-].C(C1C(C)=CC=C(O)C=1C(C)(C)C)(C)(C)C>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([C:22]2[CH:27]=[N:26][CH:25]=[CH:24][N:23]=2)[C:7]([C:11]([F:14])([F:13])[F:12])=[CH:6][C:5]=1[NH2:15]

참가 물질

7

반응물 4

HCID 433294Lithium ChlorideHCID 27373162-(Tributylstannyl)pyrazineHCID 3034427Phenol, bis(1,1-dimethylethyl)-4-methyl-HCID 53436880Methyl 2-amino-5-iodo-4-(trifluoromethyl)benzoate

생성물 1

HCID 119657822-Amino-5-pyrazin-2-yl-4-trifluoromethyl-benzoic acid methyl ester수율 38.4%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매2회HCID 312751,4-Dioxane용매

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온도
120 °C

실험 절차

A solution containing 2-amino-5-iodo-4-trifluoromethyl-benzoic acid methyl ester (750 mg, 2.17 mmol), 2-tributylstannylpyrazine (1.0 g, 2.7 mmol) and (Ph3P)4Pd (125.6 mg, 0.109 mmol) in dioxane (40 mL) was heated at 120° C. for 17 h. LiCl (276.4 mg, 6.5 mmol) was added and the reaction mixture was refluxed for 1.5 h prior to the addition of di-t-butyl-p-cresol (188 mg, 0.85 mmol) and another portion of (Ph3P)4Pd (251.2 mg, 0.22 mmol). Heating was continued for 16 h, for a total reaction time of 36 h. After cooling to r.t., the solvent was removed in vacuo and the residue was purified by flash chromatography (200 g silica gel, hexanes→EtOAc:hexanes (3:7 to 1:1)). The fractions containing the product were combined and concentrated in vacuo. The resultant oil was further purified by partitioning between CH3CN and hexanes. The acetonitrile layer was concentrated in vacuo to furnish the title compound (248 mg, 38%) as a solid. API-ES: m/z 298 [M+H]+, rt 4.18 min.

후처리

  1. temperaturethe reaction mixture was refluxed for 1.5 h
  2. temperatureHeating
  3. temperatureAfter cooling to r.t.
  4. customthe solvent was removed in vacuo
  5. customthe residue was purified by flash chromatography (200 g silica gel, hexanes→EtOAc:hexanes (3:7 to 1:1))
  6. additionThe fractions containing the product
  7. concentrationconcentrated in vacuo
  8. customThe resultant oil was further purified
  9. customby partitioning between CH3CN and hexanes
  10. concentrationThe acetonitrile layer was concentrated in vacuo

출처 및 근거

ORD 기록
ord-ddf1725357c042f9bab24c11b03981ce
출처 데이터셋
uspto-grants-2010_02
특허 번호
US07655666B2

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