ethyl 5-((tert-butoxycarbonyl(2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-4-yl)amino)methyl)-1,3,4-thiadiazole-2-carboxylate → Methyl 5-((2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-4-ylamino)methyl)-1,3,4-thiadiazole-2-carboxylate

HRID 2175415Notes

Reaction equation

HRID 2175415 reaction equation
C(OC([N:8]([CH2:28][C:29]1[S:33][C:32]([C:34]([O:36][CH2:37]C)=[O:35])=[N:31][N:30]=1)[C:9]1[CH:14]=[C:13]([O:15][CH2:16][C@H:17]2[CH2:19][C@@H:18]2[C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][N:21]=2)[N:12]=[C:11]([CH3:27])[N:10]=1)=O)(C)(C)C>C(O)(C(F)(F)F)=O>[CH3:27][C:11]1[N:10]=[C:9]([NH:8][CH2:28][C:29]2[S:33][C:32]([C:34]([O:36][CH3:37])=[O:35])=[N:31][N:30]=2)[CH:14]=[C:13]([O:15][CH2:16][C@H:17]2[CH2:19][C@@H:18]2[C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][N:21]=2)[N:12]=1

Participants

3

Reactant 1

HCID 86729573ethyl 5-((tert-butoxycarbonyl(2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-4-yl)amino)methyl)-1,3,4-thiadiazole-2-carboxylate

Product 1

HCID 71274155Methyl 5-((2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-4-ylamino)methyl)-1,3,4-thiadiazole-2-carboxylateYield 45.3%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

The solution of ethyl 5-((tert-butoxycarbonyl(2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-4-yl)amino)methyl)-1,3,4-thiadiazole-2-carboxylate (S-7) (70 mg, 0.1294 mmol) in TFA (1 mL) was stirred at room temperature for 1 h. The solvent was removed under reduced pressure and the residue was purified by reverse phase column (Waters Sunfire Prep C18 OBD, 5-75% methanol in water with 0.1% NH3H2O modifier) to provide product as a white solid (25 mg, 21.4%). 1H NMR (400 MHz, CDCl3) δ 8.26 (s, 1H), 7.35 (dd, J=7.9, 1.7 Hz, 1H), 7.03 (d, J=7.9 Hz, 1H), 5.60 (s, 1H), 5.48 (s, 1H), 5.02 (d, J=6.3 Hz, 1H), 4.27 (ddd, J=24.1, 11.1, 7.0 Hz, 2H), 4.03 (s, 3H), 2.48 (d, J=5.8 Hz, 3H), 2.19 (s, 3H), 1.87-1.85 (m, 1H), 1.85-1.80 (m, 1H), 1.32-1.29 (m, 1H), 1.06-1.02 (m, 1H); LRMS (ESI) calculated M+H for C20H23N6O3S: 427.5. Found: 427.1.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was purified by reverse phase column (Waters Sunfire Prep C18 OBD, 5-75% methanol in water with 0.1% NH3H2O modifier)

Sources & evidence

ORD record
ord-6ee10dfa345f4475a4cea44e1c8418da
Source dataset
uspto-grants-2015_06
Patent number
US09062059B2

Reaction notes

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