Potassium Phosphate, Tribasic → HCID 86687483, compound

HRID 1473438Notes

Reaction equation

HRID 1473438 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]([O:28][CH3:29])[CH:3]=1.[C:30]([C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1)#[N:31].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CC(OC)(C)C.COC1C=CC=C(OC)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1.C1C=[C-]C(CCN)=CC=1.Cl[Pd+]>[C:30]([C:32]1[CH:37]=[C:36]([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]([O:28][CH3:29])[CH:3]=2)[CH:35]=[CH:34][CH:33]=1)#[N:31]

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27343253-Cyanophenylboronic acidHCID 866874841-(4-chloro-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

Product 1

HCID 86687483HCID 86687483, compoundYield 60.2%

Reagents, catalysts & solvents 1

HCID 71311105SPhos PalladacycleCatalyst

Conditions

Temperature
120 °C

Procedure

A microwave vial was charged with 1-(4-chloro-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (53.42 mg, 0.125 mmol), (3-cyanophenyl)boronic acid (55.2 mg, 0.375 mmol), potassium phosphate (106 mg, 0.501 mmol), and chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(II) methyl-t-butylether adduct (Strem Chemical, Newburyport, Mass.) (9.52 mg, 0.013 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (501 μl) and water (125 μl) were added. The vial was sealed and heated to 120° C. for 30 min in a microwave reactor. The mixture was extracted with EtOAc (3×). The combined organic extracts were concentrated. The crude product was purified by chromatography on silica gel (0 to 10% MeOH/DCM) to give 1-(3′-cyano-3-methoxy-[1,1′-biphenyl]-4-yl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (37.15 mg, 0.075 mmol, 60.2% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=13.00 (br. s., 1H), 8.70 (d, J=5.7 Hz, 1H), 8.66 (d, J=1.4 Hz, 1H), 8.58 (s, 1H), 8.37 (d, J=1.6 Hz, 1H), 8.30-8.17 (m, 2H), 8.15-8.05 (m, 1H), 8.01-7.94 (m, 1H), 7.92-7.86 (m, 1H), 7.81-7.70 (m, 2H), 7.60-7.43 (m, 3H), 7.03 (d, J=6.5 Hz, 1H), 3.78 (s, 3H); m/z (ESI) 494.2 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (501 μl) and water (125 μl) were added
  3. customThe vial was sealed
  4. extractionThe mixture was extracted with EtOAc (3×)
  5. concentrationThe combined organic extracts were concentrated
  6. customThe crude product was purified by chromatography on silica gel (0 to 10% MeOH/DCM)

Sources & evidence

ORD record
ord-1e54689e977e454a9a8fc7ad7c1edd5e
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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