Sodium Carbonate → HCID 22317669, compound

HRID 498247Notes

Reaction equation

HRID 498247 reaction equation
CO[C:3](=[O:27])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[CH:15]=[C:14]([CH3:16])[N:13]=[C:12]([NH:17][CH2:18][CH2:19][O:20]C3CCCCO3)[N:11]=2)[CH:5]=1.[C:28]([C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1)([OH:30])=[O:29].[Cl:40][C:41]1[N:46]=[C:45](Cl)[CH:44]=[C:43]([CH3:48])[N:42]=1.[C:49]([O-:52])([O-])=[O:50].[Na+].[Na+]>C(#N)C.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>[C:31]([O:52][C:49](=[O:50])[CH2:41][C:3]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[CH:15]=[C:14]([CH3:16])[N:13]=[C:12]([NH:17][CH2:18][CH2:19][OH:20])[N:11]=2)[CH:5]=1)=[O:27])([CH3:28])([CH3:36])[CH3:32].[Cl:40][C:41]1[N:46]=[C:45]([C:33]2[CH:32]=[C:31]([CH:36]=[CH:35][CH:34]=2)[C:28]([OH:30])=[O:29])[CH:44]=[C:43]([CH3:48])[N:42]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 794712,4-Dichloro-6-methylpyrimidineHCID 27339573-Carboxyphenylboronic acidHCID 69486958HCID 69486958, compound

Product 2

HCID 22317669HCID 22317669, compoundHCID 69489740HCID 69489740, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
85 °C

Procedure

The title compound was prepared from rac-3-{6-methyl-2-[2-(tetrahydro-pyran-2-yloxy)-ethylamino]-pyrimidin-4-yl}-benzoic acid methyl ester [prepared by the following procedure: A mixture of 3-carboxyphenylboronic acid (8.3 g, 50.0 mmol), 2,4-dichloro-6-methylpyrimidine (8.15 g, 50.0 mmol) and Na2CO3 (9.5 g, 90 mmol) in acetonitrile (160 ml)/H2O (80 ml) was degassed and Pd(PPh3)4 (0.87 g, 0.75 mmol) was added. The mixture was stirred for 18 h at 85° C. in an atmosphere of nitrogen and then concentrated in vacuum to a volume of ca.100 ml H2O (100 ml) was added and the mixture was washed with AcOEt (50 ml). The pH of the aqueous phase was set to 2.5 by addition of 25% HCl and the precipitate was collected and dried to give 3-(2-chloro-6-methyl-pyrimidin-4-yl)-benzoic acid (9.1 g) as a white solid. A sample of this material (1.49 g, 6 mmol) was heated in 2-amino-ethanol (3.6 ml) at 80° C. for 1 h. The mixture was evaporated in vacuum and the residual oil was stirred in 1N HCl-MeOH (20 ml) for 18 h at 40° C. The crude product (1.36 g) and 3,4-dihydro-2H-pyran (0.86 ml, 9.5 mmol) were stirred in AcOEt (10 mL)/4N HCl-Et2O (1.3 ml) for 4 h at RT The mixture was diluted with AcOEt and washed with sat. NaHCO3-sol. and brine. The organic layer was dried over Na2SO4, evaporated in vacuum, and the residue was purified by chromatography (silica gel, AcOEt/hexane 1:1) to give the methyl ester as light yellow oil (1.53 g).] (1.53 g, 4.1 mmol) by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a light yellow oil (1.62 g).

Workup

  1. customprepared by the following procedure
  2. customwas degassed
  3. concentrationconcentrated in vacuum to a volume of ca
  4. addition100 ml H2O (100 ml) was added
  5. washthe mixture was washed with AcOEt (50 ml)
  6. additionThe pH of the aqueous phase was set to 2.5 by addition of 25% HCl
  7. customthe precipitate was collected
  8. customdried

Sources & evidence

ORD record
ord-6ef870ef83f847e7bea6259c239fc11d
Source dataset
uspto-grants-2005_09
Patent number
US06949542B2

Reaction notes

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