Water → 4-(7-Amino-6-bromo-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-hydroxycyclohexanecarboxylic acid

HRID 334362Notes

Reaction equation

HRID 334362 reaction equation
C[Si](C)(C)CCOC[N:7](COCC[Si](C)(C)C)[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:21][CH:22]=3)=[C:12]2[N:11]=[C:10]([CH:29]2[CH2:34][CH2:33][C:32](=[O:35])[CH2:31][CH2:30]2)[C:9]=1[Br:36].Br[CH:48](Br)Br.[OH-:51].[K+].[OH2:53]>CC#N.O>[NH2:7][C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20]([C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)=[CH:21][CH:22]=3)=[C:12]2[N:11]=[C:10]([CH:29]2[CH2:30][CH2:31][C:32]([OH:35])([C:48]([OH:53])=[O:51])[CH2:33][CH2:34]2)[C:9]=1[Br:36]

Participants

6

Reactant 4

HCID 962WaterHCID 5558BromoformHCID 14797Potassium HydroxideHCID 866866634-(7-(Bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-bromo-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexanone

Product 1

HCID 568485284-(7-Amino-6-bromo-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-hydroxycyclohexanecarboxylic acid

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

To an ice-cooled mixture of 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-bromo-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexanone (125 mg, 0.173 mmol) and tribromomethane (151 uL, 1.73 mmol) in CH3CN/H2O (1/0.5 mL) was added a solution of KOH in H2O (87.3 mg, 1.56 mmol, 1 g/mL) dropwise during 5 min. The resulting reaction mixture was stirred vigorously at rt overnight. All the volatiles were removed and the residue was treated with TFA/H2O (1/1 mL) overnight. After removal of TFA/H2O, the crude product was purified by a reverse phase HPLC to afford 4-(7-amino-6-bromo-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-hydroxycyclohexanecarboxylic acid (Compound 131) as a pale yellow solid (5.0 mg). HPLC-MS TR=1.52 min (UV 254 nm, 5 min method); mass calculated for formula C24H22BrN5O3 507.1, observed LCMS m/z 508.0 (M+H).

Workup

  1. customThe resulting reaction mixture
  2. customAll the volatiles were removed
  3. additionthe residue was treated with TFA/H2O (1/1 mL) overnight
  4. customAfter removal of TFA/H2O
  5. customthe crude product was purified by a reverse phase HPLC

Sources & evidence

ORD record
ord-a244fbf627bb4091942e146f26e5bc0a
Source dataset
uspto-grants-2014_11
Patent number
US08883801B2

Reaction notes

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