Hydrochloric Acid → 2,2-Dimethyl 4-{4'-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}4-oxobutanoic acid

HRID 907742

반응식

HRID 907742 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14](=[O:23])[CH2:15][C:16]([CH3:22])([CH3:21])[C:17]([O:19]C)=[O:18])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH3:24][C:25]1[CH:37]=[CH:36][C:28]2[N:29]=[C:30](S(C)(=O)=O)[O:31][C:27]=2[CH:26]=1.[OH-].[Na+].Cl>ClC(Cl)C.CO>[CH3:21][C:16]([CH3:22])([CH2:15][C:14]([C:11]1[CH:10]=[CH:9][C:8]([C:5]2[CH:4]=[CH:3][C:2]([NH:1][C:30]3[O:31][C:27]4[CH:26]=[C:25]([CH3:24])[CH:37]=[CH:36][C:28]=4[N:29]=3)=[CH:7][CH:6]=2)=[CH:13][CH:12]=1)=[O:23])[C:17]([OH:19])=[O:18]

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 21985743Methyl 4-(4'-amino-1,1'-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoateHCID 219857516-Methyl-2-(methylsulfonyl)-1,3-benzoxazole

생성물 1

HCID 112241122,2-Dimethyl 4-{4'-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}4-oxobutanoic acid수율 32.1%

시약·촉매·용매 2

HCID 887Methanol용매HCID 63651,1-Dichloroethane용매

반응 조건

온도
-85 °C

실험 절차

To a solution of methyl 4-(4′-amino-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoate (74 mg, 0.24 mmol) in dichloroethane (3 mL), 6-methyl-2-(methylsulfonyl)-1,3-benzoxazole (50 mg, 0.24 mmol) was added, and the mixture was heated at −85° C. overnight. The solvent was removed by rotary evaporation, and the residue was redissolved in DMF (5 mL). A solution of 1 N aqueous NaOH (0.72 mL, 0.72 mmol) was added, and the mixture was heated at 65° C. overnight. A solution of 1 N aqueous HCl (0.24 mL, 0.24 mmol) and methanol (5 mL) were added to the reaction mixture and the crude product was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA) to afford 2,2-dimethyl-4-{4′-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}-4-oxobutanoic acid as a white solid (32.6 mg, 32.1%). 1H NMR (300 MHz, DMSO-d6) δ 8.00-7.50 (m, 8H), 7.30 (d, 2H), 7.05 (d, 1H), 3.30 (s, 2H), 2.50 (s, 3H), 1.10 (s, 6H); LC-MS ret. time 3.53 min (method 2), m/z 429.17 (MH+).

후처리

  1. customThe solvent was removed by rotary evaporation
  2. dissolutionthe residue was redissolved in DMF (5 mL)
  3. temperaturethe mixture was heated at 65° C. overnight
  4. customthe crude product was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA)

출처 및 근거

ORD 기록
ord-aa6d1bd9da9a4b9d9b4f1e6738a932dd
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08013166B2

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