Sodium Carbonate → 5-(7-(Tert-butoxycarbonyl(cyclopropyl)amino)-3-formylpyrazolo[1,5-a]pyrimidin-5-yl)thiophene-2-carboxylic acid

HRID 624750Notes

Reaction equation

HRID 624750 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]([CH:16]2[CH2:18][CH2:17]2)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[N:5]2[N:19]=[CH:20][C:21]([CH:22]=[O:23])=[C:4]2[N:3]=1.[C:24]([C:27]1[S:28][C:29](B(O)O)=[CH:30][CH:31]=1)([OH:26])=[O:25].C([O-])([O-])=O.[Na+].[Na+]>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.COCCOC.CCO>[C:11]([O:10][C:9]([N:8]([CH:16]1[CH2:18][CH2:17]1)[C:6]1[N:5]2[N:19]=[CH:20][C:21]([CH:22]=[O:23])=[C:4]2[N:3]=[C:2]([C:29]2[S:28][C:27]([C:24]([OH:26])=[O:25])=[CH:31][CH:30]=2)[CH:7]=1)=[O:15])([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27798075-Boronothiophene-2-carboxylic acidHCID 58196421Tert-butyl 5-chloro-3-formylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropyl)carbamate

Product 1

HCID 583139645-(7-(Tert-butoxycarbonyl(cyclopropyl)amino)-3-formylpyrazolo[1,5-a]pyrimidin-5-yl)thiophene-2-carboxylic acidYield 35.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 20074477Dimethoxyethane ethanolSolvent

Conditions

Temperature
95 °C

Procedure

To tert-butyl 5-chloro-3-formylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropyl)carbamate (1 g, 2.97 mmol) in 30 mL of a 2:1 mixture of 1,2-dimethoxyethane/EtOH was added 2-carboxythiophene-5-boronic acid (766 mg, 4.45 mmol), tetrakis(triphenylphosphine)palladium(0) (171 mg, 0.148 mmol), and 2M aqueous solution of Na2CO3 (4.45 mL, 8.91 mmol). The mixture was stirred at 95° C. for 3 hours then cooled to room temperature and partitioned between 2N NaOH and ethyl acetate. The layers were separated and the aqueous layer was acidified to pH<3 with conc. HCl. The aqueous layer was extracted (3×) with methylene chloride. The combined organic layers was washed with brine, dried over MgSO4, filtered, and evaporated to dryness to provide 450 mg of 5-(7-(tert-butoxycarbonyl(cyclopropyl)amino)-3-formylpyrazolo[1,5-a]pyrimidin-5-yl)thiophene-2-carboxylic acid. Some additional material which was in the first ethyl acetate layer was purified by silica gel chromatography (0%-20% MeOH/CH2Cl2) to provide another 550 mg of 5-(7-(tert-butoxycarbonyl(cyclopropyl)amino)-3-formylpyrazolo[1,5-a]pyrimidin-5-yl)thiophene-2-carboxylic acid (79%). LCMS (M+1=429)

Workup

  1. temperaturethen cooled to room temperature
  2. custompartitioned between 2N NaOH and ethyl acetate
  3. customThe layers were separated
  4. extractionThe aqueous layer was extracted (3×) with methylene chloride
  5. washThe combined organic layers was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-680c73112f58481aba980bd4f83c6e1c
Source dataset
uspto-grants-2016_04
Patent number
US09303033B2

Reaction notes

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