Tetrahydrofuran → HCID 58456383, compound

HRID 410607Notes

Reaction equation

HRID 410607 reaction equation
[CH3:1][C:2]([CH3:31])([CH2:7][C:8]1[S:9][C:10]([C:13]2[CH:18]=[C:17]([NH:19][C:20]3[N:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][N:21]=3)[CH:16]=[C:15]([CH3:30])[CH:14]=2)=[CH:11][N:12]=1)[C:3]([O:5]C)=[O:4].C1COCC1.[OH-].[K+]>CO>[CH3:1][C:2]([CH3:31])([CH2:7][C:8]1[S:9][C:10]([C:13]2[CH:18]=[C:17]([NH:19][C:20]3[N:25]=[C:24]([C:26]([F:29])([F:27])[F:28])[CH:23]=[CH:22][N:21]=3)[CH:16]=[C:15]([CH3:30])[CH:14]=2)=[CH:11][N:12]=1)[C:3]([OH:5])=[O:4]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14797Potassium Hydroxide2×HCID 58456278HCID 58456278, compound

Product 1

HCID 58456383HCID 58456383, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Methyl 2,2-dimethyl-3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propanoate (278 mg, 0.617 mmol) was taken up in MeOH (4 mL)/THF (4 mL), and 1 M KOH (648 μL, 0.648 mmol) was added. The reaction was stirred at room temperature overnight. LC/MS analysis showed only ˜40% conversion, so additional 1 M KOH (123 μL, 0.123 mmol) was added, and the reaction was stirred at 50° C. overnight. The reaction was subsequently evaporated to dryness, providing 2,2-dimethyl-3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propanoic acid (potassium salt) as a yellow solid that was used without purification in subsequent reactions (337 mg, 87% pure, 100% yield). A small portion (40 mg) was purified by reverse phase HPLC (50-100% MeCN/water w/0.025% TFA). Product fractions were combined and evaporated to provide a clean sample of 2,2-dimethyl-3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}-phenyl)-1,3-thiazol-2-yl]propanoic acid (TFA salt) as an off-white foam (28 mg). MS ESI: [M+H]+ m/z 437.0. 1H NMR (600 MHz, DMSO-d6) δ 12.41 (s, 1H), 10.23 (s, 1H), 8.80 (d, J=4.9, 1H), 7.98-7.86 (m, 2H), 7.44 (s, 1H), 7.26 (d, J=4.9, 1H), 7.11 (s, 1H), 3.16 (s, 2H), 2.29 (s, 3H), 1.16 (s, 6H). rhSYK activity=+++

Workup

  1. additionwas added
  2. additionwas added
  3. stirringthe reaction was stirred at 50° C. overnight
  4. customThe reaction was subsequently evaporated to dryness

Sources & evidence

ORD record
ord-03ef85255b9e4f4d87ffbaac7a873c87
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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