Cesium carbonate → 5-(4-Chloro-phenyl)-4-(4-hydroxymethyl-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1h-pyrrole-3-carboxylic acid ethyl ester

HRID 1913398

반응식

HRID 1913398 반응식
[CH2:1]([O:3][C:4]([C:6]1[C:10](I)=[C:9]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[N:8]([C:19]2[CH:24]=[CH:23][C:22]([S:25](=[O:28])(=[O:27])[NH2:26])=[CH:21][CH:20]=2)[C:7]=1[CH3:29])=[O:5])[CH3:2].[OH:30][CH2:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C(O)C.CCOCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:10]([C:35]2[CH:36]=[CH:37][C:32]([CH2:31][OH:30])=[CH:33][CH:34]=2)=[C:9]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[N:8]([C:19]2[CH:24]=[CH:23][C:22]([S:25](=[O:28])(=[O:27])[NH2:26])=[CH:21][CH:20]=2)[C:7]=1[CH3:29])=[O:5])[CH3:2]

참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 248942295-(4-Chloro-phenyl)-4-iodo-2-methyl-1-(4-sulfamoyl-phenyl)-1h-pyrrole-3-carboxylic acid ethyl ester

생성물 1

HCID 248942275-(4-Chloro-phenyl)-4-(4-hydroxymethyl-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1h-pyrrole-3-carboxylic acid ethyl ester

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 702Ethanol용매HCID 3283Diethyl Ether용매

반응 조건

온도
110 °C

실험 절차

To a mixture of Example 96 (33 mg, 0.060 mmol), 4-(hydroxymethyl)phenylboronic acid (12 mg, 0.080 mmol), palladium acetate (2.2 mg, 0.010 mmol) suspended in ethanol (0.50 mL) was added 1 M aqueous Cs2CO3 (0.080 mL, 0.080 mmol), and heated in a microwave (Personal Chemistry: Emrys Creator) at 110° C. for 15 minutes. The mixture was diluted with Et2O (2 mL), stirred thoroughly, filtered through diatomaceous earth with Et2O rinse. The filtrate was washed with 1 M pH 7 potassium phosphate buffer, dried (Na2SO4), filtered and concentrated under reduced pressure and the residue chromatographed on an Alltech silica column (average pore size 60 Å, particle size 50 μM) (30→10% hexanes/Et2O) to provide a white foam. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.81 (d, 2H), 7.49 (d, 2H), 7.48 (bs, 2H), 7.14 (d, 2H), 7.14 (d, 2H), 7.06 (d, 2H), 6.95 (d, 2H), 5.10 (t, 1H), 4.45 (d, 2H), 4.02 (q, 2H), 2.32 (s, 3H), 1.0 (t, 3H); MS (ESI) m/z m/z 525/527.

후처리

  1. filtrationfiltered through diatomaceous earth with Et2O
  2. washrinse
  3. washThe filtrate was washed with 1 M pH 7 potassium phosphate buffer
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customthe residue chromatographed on an Alltech silica column (average pore size 60 Å, particle size 50 μM) (30→10% hexanes/Et2O)
  8. customto provide a white foam

출처 및 근거

ORD 기록
ord-58cbdab785cb4441977a94aee962b8f5
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08609713B2

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