Potassium Phosphate, Tribasic → HCID 86687639, compound

HRID 1473578Notes

Reaction equation

HRID 1473578 reaction equation
Cl[C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[C:18]3[C:13](=[CH:14][C:15]([S:19]([NH:22][C:23]4[S:24][CH:25]=[N:26][N:27]=4)(=[O:21])=[O:20])=[CH:16][CH:17]=3)[CH:12]=[CH:11][N:10]=2)=[C:4]([O:28][CH3:29])[CH:3]=1.[F:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>[F:8][C:7]1[CH:6]=[C:5]([C:9]2[C:18]3[C:13](=[CH:14][C:15]([S:19]([NH:22][C:23]4[S:24][CH:25]=[N:26][N:27]=4)(=[O:21])=[O:20])=[CH:16][CH:17]=3)[CH:12]=[CH:11][N:10]=2)[C:4]([O:28][CH3:29])=[CH:3][C:2]=1[C:35]1[CH:34]=[CH:33][CH:32]=[C:31]([F:30])[CH:36]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27339863-Fluorophenylboronic acidHCID 86687637HCID 86687637, compound

Product 1

HCID 86687639HCID 86687639, compoundYield 64.7%

Reagents, catalysts & solvents 1

HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalyst

Conditions

Temperature
120 °C

Procedure

A vial was charged with 1-(4-chloro-5-fluoro-2-methoxyphenyl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide (INTERMEDIATE HHHHH; 80.29 mg, 0.178 mmol), (3-fluorophenyl)boronic acid (49.8 mg, 0.356 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (1.828 mg, 4.45 μmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(ii) dichloromethane (6.74 mg, 8.90 μmol), and potassium phosphate (113 mg, 0.534 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (809 μl) and water (81 μl) were added. The vial was sealed and heated in a Biotage Initiator microwave reactor for 1 h at 120° C. The mixture was extracted with EtOAc (3×). The aq. layer was acidified with 0.5N aq. HCl, then extracted with EtOAc (2×). The combined organic extracts were concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-7.5% MeOH/DCM) to give 1-(2,3′-difluoro-5-methoxy-[1,1′-biphenyl]-4-yl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide (58.84 mg, 0.115 mmol, 64.7% yield) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=14.50 (br. s., 1H), 8.79 (s, 1H), 8.71 (d, J=5.8 Hz, 1H), 8.57 (d, J=1.8 Hz, 1H), 8.14 (d, J=5.4 Hz, 1H), 7.94-7.88 (m, 1H), 7.85-7.78 (m, 1H), 7.64-7.53 (m, 3H), 7.42-7.27 (m, 3H), 3.72 (s, 3H). m/z (ESI) 511.2 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (809 μl) and water (81 μl) were added
  3. customThe vial was sealed
  4. extractionThe mixture was extracted with EtOAc (3×)
  5. extractionextracted with EtOAc (2×)
  6. concentrationThe combined organic extracts were concentrated
  7. customThe residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-7.5% MeOH/DCM)

Sources & evidence

ORD record
ord-da05a2a23e6544408064f728e9ed9a99
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

Loading…