Hydrochloric Acid → HCID 67064797, compound

HRID 1256412Notes

Reaction equation

HRID 1256412 reaction equation
[CH3:1][C:2]([C:12]1[CH:17]=[CH:16][C:15]([C:18](=[O:36])[NH:19][C:20]2[CH:25]=[C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:23]3[N:32]=[C:33]([CH3:35])[CH:34]=[C:22]3[N:21]=2)=[CH:14][CH:13]=1)([CH3:11])[CH2:3][NH:4][C:5](=[O:10])[C:6]([O:8]C)=[O:7].[OH-].[Li+].Cl>CO>[CH3:11][C:2]([C:12]1[CH:13]=[CH:14][C:15]([C:18](=[O:36])[NH:19][C:20]2[CH:25]=[C:24]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[N:23]3[N:32]=[C:33]([CH3:35])[CH:34]=[C:22]3[N:21]=2)=[CH:16][CH:17]=1)([CH3:1])[CH2:3][NH:4][C:5](=[O:10])[C:6]([OH:8])=[O:7]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 67064478HCID 67064478, compound

Product 1

HCID 67064797HCID 67064797, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Methyl 2-(2-methyl-2-(4-(2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-ylcarbamoyl)phenyl)propylamino)-2-oxoacetate was dissolved in MeOH (1 ml). Lithium hydroxide (2 N aqueous solution, 1 ml) was then added. The mixture was stirred for 30 minutes at room temperature. Hydrochloric acid (2N aqueous solution) was added to acidify the mixture to pH 3. The reaction mixture 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 (55-65% MeCN/H2O gradient+0.01% TFA). Combined fractions were concentrated in vacuo to give a suspension. The precipitate was collected on a small fritted funnel, washed with water, and then dried under a stream of nitrogen to give the titled product (16 mg, 38% yield) as a white powder. 1H NMR (DMSO-d6) δ: 11.22 (s, 1H), 8.47 (br. s., 1H), 8.00-8.16 (m, 4H), 7.96 (s, 1H), 7.64 (d, J=2.5 Hz, 3H), 7.55 (d, J=8.6 Hz, 2H), 6.40 (s, 1H), 2.40 (s, 3H), 1.30 (s, 6H); ESI-MS: m/z 400.4 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between brine and ethyl acetate
  2. extractionthe aqueous layer was extracted one more time with ethyl acetate
  3. dry with materialCombined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by preparatory HPLC (55-65% MeCN/H2O gradient+0.01% TFA)
  7. concentrationCombined fractions were concentrated in vacuo
  8. customto give a suspension
  9. customThe precipitate was collected on a small fritted funnel
  10. washwashed with water
  11. customdried under a stream of nitrogen

Sources & evidence

ORD record
ord-8bb8ac7c20e746c2b89c85fbcf02b010
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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