Acetic Acid → HCID 86762537, compound

HRID 1623020Notes

Reaction equation

HRID 1623020 reaction equation
[C:1]([C:5]1[S:9][C:8]([C:10]([NH:12][CH:13]([C:18]2[CH:23]=[CH:22][C:21](B3OC(C)(C)C(C)(C)O3)=[CH:20][CH:19]=2)[C:14]([O:16]C)=[O:15])=[O:11])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[Br:33][C:34]1[CH:35]=[N:36][C:37](I)=[N:38][CH:39]=1.C([O-])(O)=O.[Na+].CC(O)=O>C1COCC1.CC#N>[Br:33][C:34]1[CH:35]=[N:36][C:37]([C:21]2[CH:20]=[CH:19][C:18]([CH:13]([NH:12][C:10]([C:8]3[S:9][C:5]([C:1]([CH3:3])([CH3:4])[CH3:2])=[CH:6][CH:7]=3)=[O:11])[C:14]([OH:16])=[O:15])=[CH:23][CH:22]=2)=[N:38][CH:39]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 70066515-Bromo-2-iodopyrimidineHCID 86689693HCID 86689693, compound

Product 1

HCID 86762537HCID 86762537, compoundYield 47.5%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

Prepared using General Procedure 10. A mixture of methyl 2-(5-(tert-butyl)thiophene-2-carboxamido)-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl)acetate (320 mg, 0.71 mmol) and 5-bromo-2-iodopyrimidine (220 mg, 0.78 mmol) in THF (2 mL) and MeCN (2 mL) was treated with saturated aq. NaHCO3 (1600 μl, 1.40 mmol) and de-gassed (N2 bubbling). PdCl2dppf (26 mg, 0.04 mmol) was added and the mixture was heated at 120° C. for 30 min in a microwave reactor. The mixture was poured onto H2O (30 mL), acidified with AcOH and extracted with EA (3×15 mL). The combined organics were dried over MgSO4, evaporated, and purified by chromatography (EA/hexane with 1% AcOH) to provide 160 mg (46%) of 2-(4-(5-bromopyrimidin-2-yl)phenyl)-2-(5-(tert-butyl)thiophene-2-carboxamido)acetic acid as a white solid. LCMS-ESI (m/z) calculated for C21H20BrN3O3S: 473.0; found 474.0 [M+H]+, tR=2.68 min (Method 8).

Workup

  1. customPrepared
  2. customde-gassed (N2 bubbling)
  3. additionThe mixture was poured onto H2O (30 mL)
  4. extractionextracted with EA (3×15 mL)
  5. dry with materialThe combined organics were dried over MgSO4
  6. customevaporated
  7. custompurified by chromatography (EA/hexane with 1% AcOH)

Sources & evidence

ORD record
ord-21e5ddfe7ace4625b1f1b5baeb1ffc4c
Source dataset
uspto-grants-2014_07
Patent number
US08778923B2

Reaction notes

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