Potassium Carbonate → tert-Butyl (2R)-4-({2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-1-oxo-1,2-dihydroisoquinolin-4-yl}sulfonyl)-2-(hydroxymethyl)piperazine-1-carboxylate

HRID 906451Notes

Reaction equation

HRID 906451 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][C:14]([CH3:25])([CH3:24])[CH2:15][O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[CH:6]=[C:5]2[S:26]([N:29]1[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C@@H:31]([CH2:42][OH:43])[CH2:30]1)(=[O:28])=[O:27].[CH:44]1([NH:47][C:48](=[O:66])[C:49]2[CH:54]=[C:53](B3OC(C)(C)C(C)(C)O3)[C:52]([CH3:64])=[C:51]([F:65])[CH:50]=2)[CH2:46][CH2:45]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Si:17]([O:16][CH2:15][C:14]([CH3:24])([CH3:25])[CH2:13][N:7]1[CH:6]=[C:5]([S:26]([N:29]2[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:40])([CH3:39])[CH3:41])=[O:36])[C@@H:31]([CH2:42][OH:43])[CH2:30]2)(=[O:28])=[O:27])[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:53]3[CH:54]=[C:49]([C:48](=[O:66])[NH:47][CH:44]4[CH2:45][CH2:46]4)[CH:50]=[C:51]([F:65])[C:52]=3[CH3:64])[CH:3]=2)[C:8]1=[O:12])([C:20]([CH3:22])([CH3:21])[CH3:23])([CH3:19])[CH3:18]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 21914563N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 67391011HCID 67391011, compound

Product 1

HCID 86640972tert-Butyl (2R)-4-({2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-1-oxo-1,2-dihydroisoquinolin-4-yl}sulfonyl)-2-(hydroxymethyl)piperazine-1-carboxylateYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

A solution of tert-butyl (2R)-4-{[6-bromo-2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-4-yl]sulfonyl}-2-(hydroxymethyl)piperazine-1-carboxylate (Example 49b, 0.58 g) in DMF (10 mL) was treated with N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (0.263 g), Pd-118 (0.016 g) and potassium carbonate (0.228 g). The resulting mixture was stirred at 75° C. for 6 h. The cooled reaction was concentrated under reduced pressure then purified (SiO2 chromatography, loaded in DCM, flushed with isohexane (100 mL), then DCM (200 mL), followed by a 10-100% gradient of ethyl acetate/isohexane) to afford the subtitle compound (0.537 g).

Workup

  1. customThe cooled reaction
  2. concentrationwas concentrated under reduced pressure
  3. customthen purified (SiO2 chromatography
  4. customflushed with isohexane (100 mL)

Sources & evidence

ORD record
ord-17c2cef926e54ea0a9e828edfc9f373e
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

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