Sodium Hydroxide → 2-(5-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)thiophen-2-yl)-2-oxoacetic acid

HRID 1484968Notes

Reaction equation

HRID 1484968 reaction equation
[Cl:1][C:2]1[C:3]([NH:20][C:21]2[CH:25]=[C:24]([CH:26]3[CH2:28][CH2:27]3)[NH:23][N:22]=2)=[N:4][C:5]([C:8]2[S:12][C:11]([C:13](=[O:19])[C:14]([O:16]CC)=[O:15])=[CH:10][CH:9]=2)=[N:6][CH:7]=1.[OH-].[Na+]>C(O)C>[Cl:1][C:2]1[C:3]([NH:20][C:21]2[CH:25]=[C:24]([CH:26]3[CH2:28][CH2:27]3)[NH:23][N:22]=2)=[N:4][C:5]([C:8]2[S:12][C:11]([C:13](=[O:19])[C:14]([OH:16])=[O:15])=[CH:10][CH:9]=2)=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 58169174ethyl 2-(5-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)thiophen-2-yl)-2-oxoacetate2×

Product 1

HCID 581691142-(5-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)thiophen-2-yl)-2-oxoacetic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of ethyl 2-(5-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)thiophen-2-yl)-2-oxoacetate (Compound 189) (50 mg, 0.12 mmol, 1.0 eq) in ethanol (15 mL) was added 1 N NaOH (0.5 mL, 0.48 mmol, 4.0 eq). The mixture was stirred at room temperature for 1 hour, then, concentrated and the residue was redissolved in water. To the solution was added 1N HCl (0.5 mL) and the mixture was stirred for 0.5 h at 23° C. The solution was filtered to afford 2-(5-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)thiophen-2-yl)-2-oxoacetic acid Compound 190) (30 mg, 64.3%). LC-MS (m/z): 390.0 [M+]+. 1H NMR (400 MHz, DMSO-d6): δ 0.74-0.78 (m, 2H), 0.96-1.01 (m, 2H), 1.92-1.96 (m, 1H), 6.42 (s, 1H), 7.87 (d, J=4.0 Hz, 1H), 8.07 (d, J=4.4 Hz, 1H), 8.49 (s, 1H), 9.51 (s, 1H), 13.28 (bs, 1H).

Workup

  1. concentrationconcentrated
  2. dissolutionthe residue was redissolved in water
  3. additionTo the solution was added 1N HCl (0.5 mL)
  4. stirringthe mixture was stirred for 0.5 h at 23° C
  5. filtrationThe solution was filtered

Sources & evidence

ORD record
ord-4dfe5e807f844278a1071e7c2f211fdd
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

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