Water → HCID 71548605, compound

HRID 595065Notes

Reaction equation

HRID 595065 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]2[CH3:20])[C:5]2[CH:10]([CH3:11])[S:9](=[O:13])(=[O:12])[CH2:8][C:6]=2[N:7]=1.[CH:21]1([NH:24][C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31](B3OC(C)(C)C(C)(C)O3)=[CH:30][CH:29]=2)=[O:26])[CH2:23][CH2:22]1.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:21]1([NH:24][C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([C:2]3[N:3]=[C:4]([N:14]4[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]4[CH3:20])[C:5]4[CH:10]([CH3:11])[S:9](=[O:13])(=[O:12])[CH2:8][C:6]=4[N:7]=3)=[CH:30][CH:29]=2)=[O:26])[CH2:23][CH2:22]1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 44119149N-Cyclopropyl-N'-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureaHCID 89494576HCID 89494576, compound

Product 1

HCID 71548605HCID 71548605, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-chloro-5-methyl-4-[(3S)-3-methylmorpholin-4-yl]-5,7-dihydrothieno[3,4-d]pyrimidine 6,6-dioxide (100 mg, 0.3147 mmol) in DME/H2O (2 mL, 4/1, v/v) were added 1-cyclopropyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (114.1 mg, 0.37 mmol) and sodium carbonate (100.1 mg, 0.94 mmol) The reaction was degassed twice and a catalytic amount of Pd(dppf)Cl2 (10 mg, 0.013 mmol) was added to the suspension. The mixture was heated at 80° C. for 3 h under a nitrogen atmosphere. The resulting mixture was cooled and H2O was added. The mixture was extracted with ethyl acetate and the combined organic layers washed with brine, dried over anhydrous Na2SO4, filtered, and then evaporated. The residue was purified by column chromatography on silica gel (eluent: CH2Cl2/ethyl acetate=20/1˜5/1) and preparative HPLC to provide the product as a white solid (30.0 mg, 21%).

Workup

  1. customwas degassed twice
  2. temperatureThe resulting mixture was cooled
  3. extractionThe mixture was extracted with ethyl acetate
  4. washthe combined organic layers washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by column chromatography on silica gel (eluent: CH2Cl2/ethyl acetate=20/1˜5/1) and preparative HPLC

Sources & evidence

ORD record
ord-0dc9e471f9cb42e687895c5fbbb306e0
Source dataset
uspto-grants-2016_01
Patent number
US09242993B2

Reaction notes

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