Lithium Hydroxide → HCID 67064894, compound

HRID 1256417Notes

Reaction equation

HRID 1256417 reaction equation
[CH3:1][C:2]([C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:33])[NH:16][C:17]2[CH:22]=[C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:20]3[N:29]=[C:30]([CH3:32])[CH:31]=[C:19]3[N:18]=2)=[CH:11][CH:10]=1)([CH3:8])[CH2:3][C:4]([O:6]C)=[O:5].[OH-].[Li+]>CO>[CH3:8][C:2]([C:9]1[CH:10]=[CH:11][C:12]([C:15](=[O:33])[NH:16][C:17]2[CH:22]=[C:21]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:20]3[N:29]=[C:30]([CH3:32])[CH:31]=[C:19]3[N:18]=2)=[CH:13][CH:14]=1)([CH3:1])[CH2:3][C:4]([OH:6])=[O:5]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 66897311HCID 66897311, compound

Product 1

HCID 67064894HCID 67064894, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In a 50 ml pear flask was added methyl 3-methyl-3-(4-(2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-ylcarbamoyl)phenyl)butanoate (30 mg, 0.068 mmol) in methanol (2 ml) to give a tan solution. To this mixture at room temperature, lithium hydroxide (2N solution) (2 ml, 4.0 mmol) was added. The reaction progress was carefully monitored by HPLC because hydrolysis was a significant competing side reaction. After 2.5 h, most of the starting material has been consumed. The reaction mixture was acidified to pH ˜3 with 2N HCl. The resulting suspension was partitioned between brine and ethyl acetate, and the aqueous layer was extracted one more time with ethyl acetate. Combined organic layers were dried over MgSO4, filtered and concentrated. The crude product was purified by preparatory HPLC (55-80% MeCN/H2O gradient+0.01% TFA). Lyophilization of the collected fractions gave the titled product (9.9 mg, 34% yield). 1H NMR (DMSO-d6) δ: 11.91 (s, 2H), 11.20 (s, 2H), 8.04-8.08 (m, 3H), 8.02 (d, J=8.8 Hz, 3H), 7.96 (s, 2H), 7.60-7.66 (m, 5H), 7.54 (d, J=8.8 Hz, 2H), 6.40 (s, 1H), 2.66 (s, 2H), 2.40 (s, 3H), 1.41 (s, 6H); ESI-MS: m/z 429.3 (M+H)+.

Workup

  1. customto give a tan solution
  2. customThe reaction progress was carefully monitored by HPLC because hydrolysis
  3. customside reaction
  4. custommost of the starting material has been consumed
  5. customThe resulting suspension was partitioned between brine and ethyl acetate
  6. extractionthe aqueous layer was extracted one more time with ethyl acetate
  7. dry with materialCombined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by preparatory HPLC (55-80% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-d22f1d228170406e88ad38eed8597ad1
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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