Hydrochloric Acid → 1-(4-(7-Morpholinopyrazolo[1,5-a]pyrimidin-5-ylcarbamoyl)phenyl)cyclopropanecarboxylic acid

HRID 1256382Notes

Reaction equation

HRID 1256382 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[N:12]3[N:13]=[CH:14][CH:15]=[C:11]3[N:10]=[C:9]([NH:16][C:17]([C:19]3[CH:24]=[CH:23][C:22]([C:25]4([C:28]([O:30]C)=[O:29])[CH2:27][CH2:26]4)=[CH:21][CH:20]=3)=[O:18])[CH:8]=2)[CH2:3][CH2:2]1.[OH-].[Na+].Cl>CO>[O:1]1[CH2:2][CH2:3][N:4]([C:7]2[N:12]3[N:13]=[CH:14][CH:15]=[C:11]3[N:10]=[C:9]([NH:16][C:17]([C:19]3[CH:20]=[CH:21][C:22]([C:25]4([C:28]([OH:30])=[O:29])[CH2:26][CH2:27]4)=[CH:23][CH:24]=3)=[O:18])[CH:8]=2)[CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 67064333Methyl 1-(4-(7-morpholinopyrazolo[1,5-a]pyrimidin-5-ylcarbamoyl)phenyl)cyclopropanecarboxylate2×

Product 1

HCID 670645101-(4-(7-Morpholinopyrazolo[1,5-a]pyrimidin-5-ylcarbamoyl)phenyl)cyclopropanecarboxylic acidYield 24.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Methyl 1-(4-(7-morpholinopyrazolo[1,5-a]pyrimidin-5-ylcarbamoyl)phenyl)cyclopropanecarboxylate (Compound 441, 31 mg, 0.07 mmol) was dissolved in methanol, and 1N NaOH solution (1 ml) was then added. After 8 hours at room temperature, the mixture was acidified with 2N HCl to pH 1. The mixture was concentrated in vacuo. The residue was dissolved in DMSO, and was purified by preparatory HPLC (30-65% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound (6.9 mg, 23%) as a white powder. 1H NMR (400 MHz, DMSO-d6) δ=12.67-12.24 (m, 1 H), 10.98 (s, 1 H), 8.10 (d, J=2.3 Hz, 1 H), 7.98 (d, J=8.3 Hz, 2 H), 7.47 (d, J=8.3 Hz, 2 H), 7.41 (s, 1 H), 6.37 (d, J=2.3 Hz, 1 H), 3.85 (m, 2 H), 3.74 (m, 2 H), 1.56-1.45 (m, 2 H), 1.26-1.17 (m, 2 H); ESI-MS: m/z 408.4 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in DMSO
  3. customwas purified by preparatory HPLC (30-65% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-5a843f965c8b4816bfc5e2c511193796
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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