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

HRID 1409223Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1409223
[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

Komponenten

5

Edukt 3

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

Produkt 1

HCID 670645101-(4-(7-Morpholinopyrazolo[1,5-a]pyrimidin-5-ylcarbamoyl)phenyl)cyclopropanecarboxylic acidAusbeute 24,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

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, 1H), 10.98 (s, 1H), 8.10 (d, J=2.3 Hz, 1H), 7.98 (d, J=8.3 Hz, 2H), 7.47 (d, J=8.3 Hz, 2H), 7.41 (s, 1H), 6.37 (d, J=2.3 Hz, 1H), 3.85 (m, 2H), 3.74 (m, 2H), 1.56-1.45 (m, 2H), 1.26-1.17 (m, 2H); ESI-MS: m/z 408.4 (M+H)+.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-21e544b3f3b14dfabde2cd2b8af9a00d
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08921358B2

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