Hydrochloric Acid → 4-(6-acetyl-7-amino-3-(1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylic acid

HRID 334370Notes

Reaction equation

HRID 334370 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][N:20]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH:21]=3)=[C:12]2[N:11]=[C:10]([CH:28]2[CH2:33][CH2:32][C:31]([CH2:39][OH:40])([C:34]([O:36]CC)=[O:35])[CH2:30][CH2:29]2)[C:9]=1[C:41]([O:43]CC)=[CH2:42].Cl.[Li+].[OH-]>O1CCOCC1.C1COCC1.CO.O>[C:41]([C:9]1[C:10]([CH:28]2[CH2:29][CH2:30][C:31]([CH2:39][OH:40])([C:34]([OH:36])=[O:35])[CH2:32][CH2:33]2)=[N:11][C:12]2[N:13]([N:14]=[CH:15][C:16]=2[C:17]2[CH:18]=[N:19][N:20]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH:21]=2)[C:8]=1[NH2:7])(=[O:43])[CH3:42]

Participants

6

Reactant 3

HCID 313Hydrochloric Acid2×HCID 3939Lithium HydroxideHCID 66583983ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-(1-ethoxyvinyl)-3-(1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylate

Product 1

HCID 568485294-(6-acetyl-7-amino-3-(1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylic acidYield 27.7%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

To a solution of ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-(1-ethoxyvinyl)-3-(1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylate (167 mg, 0.211 mmol) in dioxane (2 mL) was added 2 mL of HCl (4 N, aq) at 0° C. The reaction mixture was stirred at rt for 1 h, then 60° C. for 1 h. The reaction mixture was evaporated to dryness. The residue was treated with LiOH (10 eq) in THF/MeOH/H2O (2/1/1 mL) at 80° C. overnight. The reaction mixture was carefully acidified with HCl (aq) to pH=6-7, and evaporated to dryness. The crude product was purified by a reverse phase HPLC to afford 4-(6-acetyl-7-amino-3-(1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylic acid as a pale yellow solid (27.7 mg). HPLC-MS TR=4.39 min (UV 254 nm, 10 min method); mass calculated for formula C25H26N6O4 474.2, observed LCMS m/z 475 (M+H).

Workup

  1. wait60° C. for 1 h
  2. customThe reaction mixture was evaporated to dryness
  3. customevaporated to dryness
  4. customThe crude product was purified by a reverse phase HPLC

Sources & evidence

ORD record
ord-a0241c735c55470ea3538ebc31d4e8e7
Source dataset
uspto-grants-2014_11
Patent number
US08883801B2

Reaction notes

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