Lithium Hydroxide → 2-(4-(7-Amino-6-bromo-3-(quinolin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexyl)acetic acid

HRID 2047066Notes

Reaction equation

HRID 2047066 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]4[C:25]([CH:26]=3)=[CH:24][CH:23]=[CH:22][CH:21]=4)=[C:12]2[N:11]=[C:10]([CH:27]2[CH2:32][CH2:31][CH:30]([CH2:33][C:34]([O:36]CC)=[O:35])[CH2:29][CH2:28]2)[C:9]=1[Br:39].C1COCC1.[Li+].[OH-]>O>[NH2:7][C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20]4[C:25]([CH:26]=3)=[CH:24][CH:23]=[CH:22][CH:21]=4)=[C:12]2[N:11]=[C:10]([CH:27]2[CH2:28][CH2:29][CH:30]([CH2:33][C:34]([OH:36])=[O:35])[CH2:31][CH2:32]2)[C:9]=1[Br:39]

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 66733730(4-{7-[Bis-(2-trimethylsilanyl-ethoxymethyl)-amino]-6-bromo-3-quinolin-3-yl-pyrazolo[1,5-a]pyrimidin-5-yl}-cyclohexyl)-acetic acid ethyl ester

Product 1

HCID 581734442-(4-(7-Amino-6-bromo-3-(quinolin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexyl)acetic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a 20 mL scintillation vial was charged ethyl 2-(4-(7-(bis((2-(trimethylsilyl)ethoxy)-methyl)amino)-6-bromo-3-(quinolin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexyl)acetate (100 mg, 130 μmol) and 2:1 THF:H2O (10 mL). To this solution was added 1N LiOH(aq) (200 μL). The resulting reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated in vacuo and the resulting residue was dissolved in TFA and stirred at room temperature for 1 hour. This solution was concentrated in vacuo and the residue was dissolved in 3:1 DMSO:MeCN. The crude product was purified via reverse-phase preparatory HPLC to yield 2-(4-(7-amino-6-bromo-3-(quinolin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexyl)acetic acid (m+H=480.1, retention time=3.95 min (isomer 1) and 4.03 min (isomer 2))

Workup

  1. customThe resulting reaction mixture
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionthe resulting residue was dissolved in TFA
  4. stirringstirred at room temperature for 1 hour
  5. concentrationThis solution was concentrated in vacuo
  6. dissolutionthe residue was dissolved in 3:1 DMSO
  7. customThe crude product was purified via reverse-phase preparatory HPLC

Sources & evidence

ORD record
ord-e69243f2ef5940738ecfefe51a24d010
Source dataset
uspto-grants-2013_11
Patent number
US08591943B2

Reaction notes

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