Potassium Phosphate, Tribasic → HCID 86687640, compound

HRID 1473579Notes

Reaction equation

HRID 1473579 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.[N:30]1[CH:35]=[CH:34][CH:33]=[C:32](B(O)O)[CH:31]=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[C:2]([C:32]2[CH:31]=[N:30][CH:35]=[CH:34][CH:33]=2)=[CH:3][C:4]([O:28][CH3:29])=[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:20])=[O:21])=[CH:16][CH:17]=3)[CH:12]=[CH:11][N:10]=2)[CH:6]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27343783-Pyridinylboronic acidHCID 86687637HCID 86687637, compound

Product 1

HCID 86687640HCID 86687640, compoundYield 60.6%

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; 74.29 mg, 0.165 mmol) pyridin-3-ylboronic acid (24.30 mg, 0.198 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (1.691 mg, 4.12 μmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(ii) dichloromethane (6.24 mg, 8.24 μmol) and potassium phosphate (105 mg, 0.494 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (749 μl) and water (74.9 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 (4×). The combined organic extracts were concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-10% MeOH/DCM) to give 1-(5-fluoro-2-methoxy-4-(pyridin-3-yl)phenyl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide (49.13 mg, 0.100 mmol, 60.4% yield) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=14.53 (br. s., 1H), 8.93 (s, 1H), 8.78 (s, 1H), 8.71 (d, J=5.7 Hz, 1H), 8.67 (dd, J=1.3, 4.7 Hz, 1H), 8.57 (d, J=1.7 Hz, 1H), 8.14 (d, J=5.8 Hz, 2H), 7.96-7.87 (m, 1H), 7.86-7.78 (m, 1H), 7.63-7.54 (m, 1H), 7.45-7.36 (m, 2H), 3.73 (s, 3H). m/z (ESI) 494.1 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (749 μl) and water (74.9 μl) were added
  3. customThe vial was sealed
  4. extractionThe mixture was extracted with EtOAc (4×)
  5. concentrationThe combined organic extracts were concentrated
  6. customThe residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-cdb3b7b94f5747ccac7f74c207b04979
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

Loading…