Cesium carbonate → 2-(3-{6-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-methyl-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid

HRID 216214Notes

Reaction equation

HRID 216214 reaction equation
[S:1]1[C:5]([CH2:6][NH:7][C:8]2[CH:13]=[C:12](Cl)[N:11]=[C:10]([CH3:15])[N:9]=2)=[CH:4][C:3]2[CH:16]=[CH:17][CH:18]=[CH:19][C:2]1=2.[C:20]([C:23]([C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1)([CH3:25])[CH3:24])([OH:22])=[O:21].C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.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>[S:1]1[C:5]([CH2:6][NH:7][C:8]2[N:9]=[C:10]([CH3:15])[N:11]=[C:12]([C:28]3[CH:27]=[C:26]([C:23]([CH3:25])([CH3:24])[C:20]([OH:22])=[O:21])[CH:31]=[CH:30][CH:29]=3)[CH:13]=2)=[CH:4][C:3]2[CH:16]=[CH:17][CH:18]=[CH:19][C:2]1=2

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 442489972-(3-Boronophenyl)-2-methylpropanoic acidHCID 86615705Benzo[b]thiophen-2-ylmethyl-(6-chloro-2-methyl-pyrimidin-4-yl)-amine

Product 1

HCID 690687312-(3-{6-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-methyl-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acidYield 15.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

Argon is bubbled through a mixture of benzo[b]thiophen-2-ylmethyl-(6-chloro-2-methyl-pyrimidin-4-yl)-amine [247 mg, 0.81 mmol], 3-(1-carboxy-1-methyl-ethyl)-phenyl boronic acid [304 mg, 1.46 mmol, see Example 49(b) step 2], Cs2CO3 (792 mg, 2.43 mmol), and tetrakis(triphenylphosphine)palladium (0) (92 mg, 0.08 mmol) in ethylene glycol dimethyl ether (2.5 mL) and water (0.5 mL), for a period of 10 minutes. The reaction vessel is sealed and heated to 90° C. After stirring for 6 hours the heating is turned off and the mixture is allowed to cool to ambient temperature upon standing for 24 hours. The mixture is diluted with water (20 mL) and extracted twice with EtOAc (30 mL). The organic extracts are combined and dried over magnesium sulfate, filtered and concentrated to afford 2-(3-{6-[(benzo[b]thiophen-2-ylmethyl)-amino]-2-methyl-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid [51.6 mg, 14.7%, Example 72] as a solid. LCMS RT=2.27 minutes, MS: 434 (M+H).

Workup

  1. customThe reaction vessel is sealed
  2. temperatureto cool to ambient temperature
  3. waitupon standing for 24 hours
  4. extractionextracted twice with EtOAc (30 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-081aad00a08d4ab19c82a6a432053f73
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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