Methanol → HCID 131726996, compound

HRID 2219240Notes

Reaction equation

HRID 2219240 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].C(OC(=O)[N:13]([CH2:30][CH2:31][O:32][C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][C:34]=1Br)[CH2:14][CH2:15][NH:16][S:17]([C:20]1[C:21]2[CH:22]=[CH:23][N:24]=[CH:25][C:26]=2[CH:27]=[CH:28][CH:29]=1)(=[O:19])=[O:18])(C)(C)C.[F:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1B(O)O.CO.[Cl-:54].[Na+].O>CN(C=O)C.C(OCC)(=O)C>[ClH:54].[ClH:54].[F:39][C:36]1[CH:37]=[CH:38][C:33]([O:32][CH2:31][CH2:30][NH:13][CH2:14][CH2:15][NH:16][S:17]([C:20]2[C:21]3[CH:22]=[CH:23][N:24]=[CH:25][C:26]=3[CH:27]=[CH:28][CH:29]=2)(=[O:18])=[O:19])=[C:34]([C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=2[F:42])[CH:35]=1

Participants

8

Reactant 5

HCID 887MethanolHCID 10340Sodium CarbonateHCID 27343542-Fluorophenylboronic acidHCID 57417360Sodium chloride; waterHCID 58816150HCID 58816150, compound

Product 1

HCID 131726996HCID 131726996, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Aqueous sodium carbonate (0.18 mL, 2.0 M) is added to a stirred solution of [2-(2-bromo-4-fluoro-phenoxy)-ethyl]-[2-(isoquinoline-5-sulfonylamino)-ethyl]-carbamic acid tert-butyl ester (0.101 g, 0.179 mmol), 2-fluorophenyl boronic acid (26 mg, 0.19 mmol), Pd(dppb)2Cl2 (43 mg, 0.072 mmol) in DMF (3 mL)/MeOH (0.8 mL). The resultant mixture is heated at 80° C. under argon for 16 hours. At ambient temperature ethyl acetate (10 mL) and brine (3 mL) are added to the mixture, the organic layer is separated, dried, filtered and concentrated. After MPLC separation on silica (gradient 0-1% methanol in methylene chloride), 90 mg (86% yield) of the BOC-protected title compound is obtained. The precursor is dissolved in methylene chloride (10 mL), then a small stream of anhydrous HCl gas is bubbled through the solution for 1 minute. The solution is capped with a glass stopper and allowed to stir for 1 hour to form a suspension. After filtration and drying, 70 mg (86% yield) of the title compound is obtained as a solid. ESIMS: m/z 484 (M+H)+.

Workup

  1. customthe organic layer is separated
  2. customdried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customAfter MPLC separation on silica (gradient 0-1% methanol in methylene chloride)

Sources & evidence

ORD record
ord-4a394238739442fab2c0f45ea75b3272
Source dataset
uspto-grants-2008_08
Patent number
US07414063B2

Reaction notes

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