Hydrochloric Acid → HCID 86687703, compound

HRID 1473632Notes

Reaction equation

HRID 1473632 reaction equation
C(P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.[F:35][C:36]1[CH:37]=[C:38]([OH:42])[CH:39]=[CH:40][CH:41]=1.Cl[C:44]1[CH:49]=[CH:48][C:47]([C:50]2[C:59]3[C:54](=[CH:55][C:56]([S:60]([NH:63][C:64]4[CH:69]=[CH:68][N:67]=[CH:66][N:65]=4)(=[O:62])=[O:61])=[CH:57][CH:58]=3)[CH:53]=[CH:52][N:51]=2)=[C:46]([O:70][CH3:71])[CH:45]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl>O1CCOCC1>[F:35][C:36]1[CH:37]=[C:38]([CH:39]=[CH:40][CH:41]=1)[O:42][C:44]1[CH:49]=[CH:48][C:47]([C:50]2[C:59]3[C:54](=[CH:55][C:56]([S:60]([NH:63][C:64]4[CH:69]=[CH:68][N:67]=[CH:66][N:65]=4)(=[O:61])=[O:62])=[CH:57][CH:58]=3)[CH:53]=[CH:52][N:51]=2)=[C:46]([O:70][CH3:71])[CH:45]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 97433-FluorophenolHCID 62657Potassium Phosphate, TribasicHCID 11953610Di-tert-butyl[3,4,5,6-tetramethyl-2',4',6'-tris(propan-2-yl)-[1,1'-biphenyl]-2-yl]phosphaneHCID 866874841-(4-chloro-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

Product 1

HCID 86687703HCID 86687703, compoundYield 8.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
165 °C

Procedure

A microwave vial charged with di-tert-butyl(2′,4′,6′-triisopropyl-3,4,5,6-tetramethyl-[1,1′-biphenyl]-2-yl)phosphine (0.034 g, 0.070 mmol), 3-fluorophenol (0.079 g, 0.703 mmol), 1-(4-chloro-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (0.150 g, 0.351 mmol), potassium phosphate (0.298 g, 1.406 mmol), and 1.5 mL dioxane was heated to 165° C. in the microwave for 30 minutes. LC/MS showed product, so the reaction mixture was filtered through a 0.45 μm syringe filter and was treated with HCl (4N in dioxane) (0.351 ml, 1.406 mmol). After stirring for 10 minutes, the reaction mixture was concentrated. Purification of the crude residue by reverse phase column chromatography [RediSep Gold C18, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave 1-(4-(3-fluorophenoxy)-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (0.015 g, 0.030 mmol, 8.49% yield). 1H NMR (MeCN-d3) δ: 8.69 (d, J=5.7 Hz, 1H), 8.62 (s, 1H), 8.48 (s, 1H), 8.22 (d, J=6.3 Hz, 1H), 7.89-7.97 (m, 2H), 7.80-7.88 (m, 1H), 7.38-7.47 (m, 1H), 7.35 (d, J=8.2 Hz, 1H), 7.08 (d, J=5.9 Hz, 1H), 6.87-6.99 (m, 4H), 6.76 (d, J=8.3 Hz, 1H), 3.59-3.62 (m, 3H); (M+H)+=503.0.

Workup

  1. filtrationso the reaction mixture was filtered through a 0.45 μm syringe
  2. filtrationfilter
  3. concentrationthe reaction mixture was concentrated
  4. customPurification of the crude residue by reverse phase column chromatography [RediSep Gold C18, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)]

Sources & evidence

ORD record
ord-1b73384b4a224dd4bd250e91ab4a9833
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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