Potassium Phosphate, Tribasic → HCID 86687630, compound

HRID 1473568Notes

Reaction equation

HRID 1473568 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([NH:21][C:22]4[CH:27]=[CH:26][N:25]=[CH:24][N:23]=4)(=[O:20])=[O:19])=[CH:15][CH:16]=3)[CH:11]=[CH:10][N:9]=2)=[C:4]([CH3:28])[CH:3]=1.[F:29][C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>>[F:29][C:30]1[CH:35]=[C:34]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3[C:17]4[C:12](=[CH:13][C:14]([S:18]([NH:21][C:22]5[CH:27]=[CH:26][N:25]=[CH:24][N:23]=5)(=[O:19])=[O:20])=[CH:15][CH:16]=4)[CH:11]=[CH:10][N:9]=3)=[C:4]([CH3:28])[CH:3]=2)[CH:33]=[CH:32][CH:31]=1

Participants

5

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27339863-Fluorophenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 86687629HCID 86687629, compound

Product 1

HCID 86687630HCID 86687630, compoundYield 42%

Conditions

Temperature
100 °C

Procedure

A vial was charged with 1-(4-chloro-2-methylphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (EXAMPLE 357; 61.66 mg, 0.150 mmol) (3-fluorophenyl)boronic acid (42.0 mg, 0.300 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (3.08 mg, 7.50 mmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(ii) dichloromethane (11.37 mg, 0.015 mmol) and potassium phosphate (96 mg, 0.450 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (682 μl) and water (68.2 μl) were added in sequence. The vial was sealed and heated in a Biotage Initiator microwave reactor for 1 h 45 min at 100° C. The mixture was extracted with EtOAc (3×). The combined organic extracts were concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 3% MeOH/DCM) to give 1-(3′-fluoro-3-methyl-[1,1′-biphenyl]-4-yl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (29.49 mg, 0.063 mmol, 41.8% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=13.08 (br. s., 1H), 8.77-8.67 (m, 2H), 8.58 (s, 1H), 8.24 (br. s., 1H), 8.15 (d, J=5.6 Hz, 1H), 7.98 (dd, J=1.8, 8.9 Hz, 1H), 7.80-7.72 (m, 2H), 7.71-7.61 (m, 3H), 7.55 (dt, J=6.2, 8.0 Hz, 1H), 7.39 (d, J=7.9 Hz, 1H), 7.28-7.19 (m, 1H), 7.03 (br. s., 1H), 2.06 (s, 3H). m/z (ESI) 471.2 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (682 μl) and water (68.2 μl) were added in sequence
  3. customThe vial was sealed
  4. extractionThe mixture was extracted with EtOAc (3×)
  5. concentrationThe combined organic extracts were concentrated
  6. customThe residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 3% MeOH/DCM)

Sources & evidence

ORD record
ord-bf155771bb094dad8d6963fb16cb9729
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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