1,4-Dioxane → HCID 86687701, compound

HRID 1473630Notes

Reaction equation

CC1(C)C(C)(C)OB([C:9]2[O:10][C:11]([CH3:14])=[CH:12][CH:13]=2)O1.Cl[C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:32]3[C:27](=[CH:28][C:29]([S:33]([NH:36][C:37]4[CH:42]=[CH:41][N:40]=[CH:39][N:38]=4)(=[O:35])=[O:34])=[CH:30][CH:31]=3)[CH:26]=[CH:25][N:24]=2)=[C:19]([O:43][CH3:44])[CH:18]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[CH3:44][O:43][C:19]1[CH:18]=[C:17]([C:9]2[O:10][C:11]([CH3:14])=[CH:12][CH:13]=2)[CH:22]=[CH:21][C:20]=1[C:23]1[C:32]2[C:27](=[CH:28][C:29]([S:33]([NH:36][C:37]3[CH:42]=[CH:41][N:40]=[CH:39][N:38]=3)(=[O:34])=[O:35])=[CH:30][CH:31]=2)[CH:26]=[CH:25][N:24]=1

Participants

Conditions

Temperature: 150 °C

Procedure

A microwave vial charged with Pd(Amphos)2Cl2 (0.012 g, 0.018 mmol), 4,4,5,5-tetramethyl-2-(5-methylfuran-2-yl)-1,3,2-dioxaborolane (0.073 g, 0.351 mmol), 1-(4-chloro-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (From Example 160; 0.075 g, 0.176 mmol), potassium phosphate (0.149 g, 0.703 mmol), 1.5 mL dioxane and 0.25 mL water was heated to 150° C. in the microwave for 30 minutes. LC/MS showed mostly product. The aqueous layer was removed, and the reaction mixture was treated with HCl (4N in dioxane). 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 the titled compound.

Workup

customThe aqueous layer was removed
additionthe reaction mixture was treated with HCl (4N in dioxane)
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-ab8ee0710ba04895b0b2dcf2ed969f96
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09012443B2

Reaction notes

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