Sodium Hydroxide → 1-(5-{2-[(ethylcarbamoyl)amino]-5-(1H-pyrazol-1-yl)[1,2,4]triazolo[1,5-a]pyridin-7-yl}pyrimidin-2-yl)-4-methylpiperidine-4-carboxylic acid

HRID 712363Notes

Reaction equation

HRID 712363 reaction equation
[OH-].[Na+].[CH2:3]([NH:5][C:6]([NH:8][C:9]1[N:40]=[C:12]2[CH:13]=[C:14]([C:22]3[CH:23]=[N:24][C:25]([N:28]4[CH2:33][CH2:32][C:31]([CH3:39])([C:34]([O:36]CC)=[O:35])[CH2:30][CH2:29]4)=[N:26][CH:27]=3)[CH:15]=[C:16]([N:17]3[CH:21]=[CH:20][CH:19]=[N:18]3)[N:11]2[N:10]=1)=[O:7])[CH3:4]>CCO>[CH2:3]([NH:5][C:6]([NH:8][C:9]1[N:40]=[C:12]2[CH:13]=[C:14]([C:22]3[CH:23]=[N:24][C:25]([N:28]4[CH2:29][CH2:30][C:31]([CH3:39])([C:34]([OH:36])=[O:35])[CH2:32][CH2:33]4)=[N:26][CH:27]=3)[CH:15]=[C:16]([N:17]3[CH:21]=[CH:20][CH:19]=[N:18]3)[N:11]2[N:10]=1)=[O:7])[CH3:4]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 66977033Ethyl 1-(5-{2-[(ethylcarbamoyl)amino]-5-(1H-pyrazol-1-yl)[1,2,4]triazolo[1,5-a]pyridin-7-yl}pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate

Product 1

HCID 669769431-(5-{2-[(ethylcarbamoyl)amino]-5-(1H-pyrazol-1-yl)[1,2,4]triazolo[1,5-a]pyridin-7-yl}pyrimidin-2-yl)-4-methylpiperidine-4-carboxylic acidYield 24%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

A 2N aqueous solution of NaOH (5 mL) was added to a solution of ethyl 1-(5-{2-[(ethylcarbamoyl)amino]-5-(1H-pyrazol-1-yl)[1,2,4]triazolo[1,5-a]pyridin-7-yl}pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate (88 mg, 0.17 mmol) in EtOH (15 mL) at rt and was heated at 70° C. After 2 h the reaction mixture was cooled to rt and concentrated in vacuo to ˜⅓ volume. Water (10 mL) was added and the resultant solution extracted with EtOAc (2×10 mL). The aqueous was then acidified to pH 1-2 and extracted with 10% IPA/DCM (3×10 mL). The organic layers were combined and dried (MgSO4), filtered and concentrated in vacuo to give a off white solid which was purified by semi preparative HPLC to give Compound 227 as a cream solid (20 mg, 24%). 1H NMR (DMSO) δ 10.01 (s, 1H), 9.00 (d, J=2.4 Hz, 1H), 8.94 (s, 2H), 8.16-8.06 (m, 1H), 8.01 (s, 2H), 7.81 (s, 1H), 6.77-6.73 (m, 1H), 4.35 (d, J=13.5 Hz, 2H), 3.25 (s, 2H), 2.05 (d, J=12.9 Hz, 2H), 1.38 (s, 2H), 1.25 (s, 2H), 1.19 (s, 3H), 1.14 (d, J=7.2 Hz, 3H). MS: 491.1 [M+H]+.

Workup

  1. temperatureAfter 2 h the reaction mixture was cooled to rt
  2. concentrationconcentrated in vacuo
  3. additionWater (10 mL) was added
  4. extractionthe resultant solution extracted with EtOAc (2×10 mL)
  5. extractionextracted with 10% IPA/DCM (3×10 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a off white solid which
  10. customwas purified by semi preparative HPLC

Sources & evidence

ORD record
ord-61fe53800aeb45cab8e5db4d7e548109
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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