Hydrochloric Acid → (3R)-3-[({7-[(2,6-Difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridin-3-yl}carbonyl)amino]-5-methylhexanoic Acid

HRID 1486335Notes

Reaction equation

HRID 1486335 reaction equation
[F:1][C:2]1[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[C:3]=1[CH2:4][O:5][C:6]1[N:11]2[N:12]=[C:13]([CH3:31])[C:14]([C:15]([NH:17][C@H:18]([CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:19][C:20]([O:22]C(C)(C)C)=[O:21])=[O:16])=[C:10]2[CH:9]=[C:8]([CH3:32])[CH:7]=1.Cl>C(OCC)C>[F:1][C:2]1[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[C:3]=1[CH2:4][O:5][C:6]1[N:11]2[N:12]=[C:13]([CH3:31])[C:14]([C:15]([NH:17][C@H:18]([CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:19][C:20]([OH:22])=[O:21])=[O:16])=[C:10]2[CH:9]=[C:8]([CH3:32])[CH:7]=1

Participants

4

Reactant 2

HCID 313Hydrochloric Acid2×HCID 117859497tert-Butyl (3R)-3-[({7-[(2,6-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridin-3-yl}carbonyl)amino]-5-methylhexanoate

Product 1

HCID 117859755(3R)-3-[({7-[(2,6-Difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridin-3-yl}carbonyl)amino]-5-methylhexanoic AcidYield 73%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

88 mg (0.17 mmol) of tert-butyl (3R)-3-[({7-[(2,6-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridin-3-yl}carbonyl)amino]-5-methylhexanoate from Example 37 were suspended in 2 ml of diethyl ether and admixed with 2.56 ml of 2 N hydrogen chloride solution, and the mixture was stirred at RT overnight. Subsequently, 2 ml of 2 N hydrogen chloride solution in diethyl ether were added and the mixture was stirred at RT for 4 h. The reaction mixture was concentrated, admixed with water and TFA and purified by means of preparative HPLC (RP18 column, eluent:acetonitrile/water gradient with addition of 0.1% TFA). The product fractions were combined, concentrated and lyophilized. 57 mg of the target compound were obtained (73% of theory).

Workup

  1. stirringthe mixture was stirred at RT for 4 h
  2. concentrationThe reaction mixture was concentrated
  3. custompurified by means of preparative HPLC (RP18 column, eluent:acetonitrile/water gradient with addition of 0.1% TFA)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-bb778877539c47babfed0d53fd97a186
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

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