Ammonium Chloride → 4-methyl-N-(3-phenoxy-5-(1-(piperidin-4-yl)ethylthio)pyridin-2-yl)thiazol-2-amine bis(2,2,2-trifluoroacetate)

HRID 335161Notes

Reaction equation

HRID 335161 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:8][C:9]([F:14])([F:13])[C:10]([OH:12])=[O:11].S1C=CN=C1N.[CH3:21][C:22]1[N:23]=[C:24]([NH:27][C:28]2[N:33]=[CH:32][C:31]([S:34]CCC(OC)=O)=[CH:30][C:29]=2[O:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[S:25][CH:26]=1.CC([O-])(C)C.[K+].CS(O[CH:59]([CH:61]1[CH2:66][CH2:65][N:64](C(OC(C)(C)C)=O)[CH2:63][CH2:62]1)[CH3:60])(=O)=O.[NH4+].[Cl-]>C1COCC1>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:8][C:9]([F:14])([F:13])[C:10]([OH:12])=[O:11].[CH3:21][C:22]1[N:23]=[C:24]([NH:27][C:28]2[C:29]([O:41][C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)=[CH:30][C:31]([S:34][CH:59]([CH:61]3[CH2:62][CH2:63][NH:64][CH2:65][CH2:66]3)[CH3:60])=[CH:32][N:33]=2)[S:25][CH:26]=1

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 232828864-[1-[(Methylsulfonyl)oxy]ethyl]-1-piperidinecarboxylic acid 1,1-dimethylethyl esterHCID 23665647Potassium tert-butoxideHCID 24765636Methyl 3-(6-(4-methylthiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)propanoateHCID 86678231HCID 86678231, compound

Product 1

HCID 866782304-methyl-N-(3-phenoxy-5-(1-(piperidin-4-yl)ethylthio)pyridin-2-yl)thiazol-2-amine bis(2,2,2-trifluoroacetate)Yield 14.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Preparation of 4-methyl-N-(3-phenoxy-5-(1-piperidin-4-yl)ethylthio)pyridin-2-yl)thiazol-2-amine bis(2,2,2-trifluoroacetate): A nitrogen purged vial was charged with methyl 3-(6-(4-methylthiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)propanoate (0.150 g, 0.374 mmol) and THF (5 mL). Potassium 2-methylpropan-2-olate (0.934 mL, 0.934 mmol) was added and stirred at ambient temperature for 30 seconds. Tert-butyl 4-(1-(methylsulfonyloxy)ethyl)piperidine-1-carboxylate (0.144 g, 0.467 mmol) was added and stirred at ambient temperature under nitrogen for 20 hours. Saturated NH4Cl was added and extracted with CH2Cl2. The organic layer was dried, filtered, and concentrated. The residue was dissolved in CH2Cl2 (5 mL) and TFA (2 mL) was added and stirred for 1 hour. The reaction was concentrated and purified by reverse phase chromatography (with 0.1% TFA) to provide the title compound (0.0363 g, 14.8% yield). 1H NMR (d6-DMSO) δ 8.57 (bs, 1H), 8.23 (bs, 1H), 8.18 (d, 1H), 7.42 (t, 2H), 7.34 (d, 1H), 7.19 (t, 1H), 7.07 (d, 2H), 6.64 (s, 1H), 3.26 (d, 2H), 3.13 (m, 1H), 2.80 (m, 2H), 2.24 (s, 3H), 1.87 (m, 2H), 1.67 (m, 1H), 1.47 (m, 2H), 1.15 (d, 3H).

Workup

  1. stirringstirred at ambient temperature under nitrogen for 20 hours
  2. extractionextracted with CH2Cl2
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in CH2Cl2 (5 mL)
  7. additionTFA (2 mL) was added
  8. stirringstirred for 1 hour
  9. concentrationThe reaction was concentrated
  10. custompurified by reverse phase chromatography (with 0.1% TFA)

Sources & evidence

ORD record
ord-b8b5d9b13f4240ceb75398136033cca4
Source dataset
uspto-grants-2014_11
Patent number
US08883828B2

Reaction notes

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