Potassium Carbonate → HCID 178497582, compound

HRID 707305Notes

Reaction equation

HRID 707305 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]2[CH2:12][C@H:11]([NH:13][C:14]3[N:23]=[CH:22][C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[N:15]=3)[CH2:10]2)[C:3]=1[NH2:24].[CH3:25][O:26][C:27]([C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1)=[O:28].C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[NH2:24][C:3]1[C:2]([C:32]2[CH:33]=[CH:34][C:29]([C:27]([O:26][CH3:25])=[O:28])=[CH:30][CH:31]=2)=[N:7][CH:6]=[N:5][C:4]=1[NH:8][C@H:9]1[CH2:12][C@H:11]([NH:13][C:14]2[N:23]=[CH:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=2)[CH2:10]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 27343694-Methoxycarbonylphenylboronic acidHCID 178507848HCID 178507848, compound

Product 1

HCID 178497582HCID 178497582, compoundYield 67.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

6-chloro-N4-(trans-3-(quinazolin-2-ylamino)cyclobutyl)pyrimidine-4,5-diamine (from example 13 step 2, 0.045 g, 0.132 mmol), tetrakis(triphenylphosphine)palladium (0.015 g, 0.013 mmol), (4-methoxycarbonylphenyl)boronic acid (0.036 g, 0.197 mmol), and potassium carbonate (0.073 g, 0.527 mmol) were combined with dioxane (2 mL) and water (0.5 mL) and sealed in a vial under argon. The reaction was heated at 120° C. for 25 minutes in the microwave. The crude product was partitioned between water (100 mL) and ethyl acetate (100 mL) and the organic phase dried with magnesium sulfate. Purification using silica chromatography (0-8% (2N ammonia in methanol) in dichloromethane) gave the desired methyl 4-(5-amino-6-((trans-3-(quinazolin-2-ylamino)cyclobutyl)amino)pyrimidin-4-yl)benzoate (0.039 g, 0.088 mmol, 67.1% yield) as a yellow oil.

Workup

  1. customsealed in a vial under argon
  2. customThe crude product was partitioned between water (100 mL) and ethyl acetate (100 mL)
  3. dry with materialthe organic phase dried with magnesium sulfate
  4. customPurification

Sources & evidence

ORD record
ord-64b5128800ab44728f7233abe80e8c43
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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