Potassium Carbonate → HCID 67199869, compound

HRID 1948741Notes

Reaction equation

HRID 1948741 reaction equation
Cl[C:2]1[C:11]([CH2:12][OH:13])=[CH:10][C:9]2[C:4](=[C:5]([CH3:15])[CH:6]=[CH:7][C:8]=2[Cl:14])[N:3]=1.[C:16]1([CH3:25])[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1B(O)O.C([O-])([O-])=O.[K+].[K+].[H-].[Na+].[NH2:34][C:35]1[N:40]=[C:39](Cl)[CH:38]=[C:37]([CH3:42])[N:36]=1>COCCOC.O.CCOC(C)=O.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>[Cl:14][C:8]1[CH:7]=[CH:6][C:5]([CH3:15])=[C:4]2[C:9]=1[CH:10]=[C:11]([CH2:12][O:13][C:39]1[CH:38]=[C:37]([CH3:42])[N:36]=[C:35]([NH2:34])[N:40]=1)[C:2]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[CH3:25])=[N:3]2

Participants

10

Reactant 5

HCID 11430Potassium CarbonateHCID 218102-Amino-4-chloro-6-methylpyrimidineHCID 24758Sodium hydrideHCID 27332672-Methylphenyl boronic acidHCID 24276151(2,5-Dichloro-8-methylquinolin-3-yl)methanol

Product 1

HCID 67199869HCID 67199869, compoundYield 12%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (2,5-dichloro-8-methylquinolin-3-yl)methanol (500 mg, 2.06 mmol), o-tolylboronic acid (337 mg, 2.48 mmol) and K2CO3 (428 mg, 3.09 mmol) in DME (8 mL) and water (2 mL) was degassed for 5 minutes. Pd(PPh3)4 (119 mg, 0.1 mmol) was added and the reaction mixture was degassed for a further 5 minutes then heated to 120° C. under microwave irradiation for 1 h. The solvent was removed in vacuo and the residue was dissolved in DMF (30 mL). To this solution was added sodium hydride (60% in mineral oil, 102 mg, 4.27 mmol) and the mixture was stirred at r.t. for 30 minutes. 2-Amino-4-chloro-6-methylpyrimidine (490 mg, 3.41 mmol) was added and the mixture was stirred at r.t. for 18 h. The mixture was diluted with EtOAc (150 mL) and washed with water (7×30 mL). The organic layer was separated, dried (MgSO4) and the solvent removed in vacuo. Purification by column chromatography (SiO2, 0-5% MeOH in DCM) then by preparative HPLC (Method 1) gave the title compound as a white solid (100 mg, 12%). δH (CDCl3) 8.72 (s, 1H), 7.44-7.55 (m, 2H), 7.24-7.36 (m, 4H), 5.99 (s, 1H), 5.27 (s, 2H), 4.92 (br s, 2H), 2.73 (s, 3H), 2.24 (s, 3H), 2.18 (s, 3H). LCMS (ES+) 405.1, 407.0 (M+H)+, RT 2.91 minutes (Method 3).

Workup

  1. customwas degassed for 5 minutes
  2. customthe reaction mixture was degassed for a further 5 minutes
  3. customThe solvent was removed in vacuo
  4. dissolutionthe residue was dissolved in DMF (30 mL)
  5. stirringthe mixture was stirred at r.t. for 18 h
  6. washwashed with water (7×30 mL)
  7. customThe organic layer was separated
  8. dry with materialdried (MgSO4)
  9. customthe solvent removed in vacuo
  10. customPurification by column chromatography (SiO2, 0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-e2f8ac266e6c4aad81eac6f2b59520e6
Source dataset
uspto-grants-2013_03
Patent number
US08399483B2

Reaction notes

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