Tert-Butyl 6-((2-tert-butoxy-3-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-4-yl((5-methyl-1,3,4-thiadiazol-2-yl)methyl)carbamate → 6-((2-Tert-butoxy-3-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-2-methyl-N-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)pyrimidin-4-amine

HRID 2175425Notes

Reaction equation

HRID 2175425 reaction equation
[C:1]([O:5][CH:6]1[CH:8]([C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][N:10]=2)[CH:7]1[CH2:16][O:17][C:18]1[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([N:25]([CH2:33][C:34]2[S:35][C:36]([CH3:39])=[N:37][N:38]=2)C(=O)OC(C)(C)C)[CH:19]=1)([CH3:4])([CH3:3])[CH3:2]>C(O)(C(F)(F)F)=O>[C:1]([O:5][CH:6]1[CH:8]([C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][N:10]=2)[CH:7]1[CH2:16][O:17][C:18]1[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([NH:25][CH2:33][C:34]2[S:35][C:36]([CH3:39])=[N:37][N:38]=2)[CH:19]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

3

Reactant 1

HCID 86729577Tert-Butyl 6-((2-tert-butoxy-3-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-4-yl((5-methyl-1,3,4-thiadiazol-2-yl)methyl)carbamate

Product 1

HCID 781013336-((2-Tert-butoxy-3-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-2-methyl-N-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)pyrimidin-4-amineYield 65.4%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

The solution of 12-7 (41 mg, 0.074 mmol) in TFA (0.5 mL) was stirred for 1 h at rt. The excess TFA was removed under reduced pressure. The residue was dissolved in dichloromethane (10 mL) and adjusted to pH=9-10 with saturated NaHCO3 aqueous solution. The mixture was extracted with EtOAc, dried over sodium sulfate, concentrated under reduced pressure and purified by reverse phase column (Waters Sunfire Prep C18 OBD, 5-95% methanol in water with 0.1% NH3H2O modifier). The product was obtained as a white solid (22 mg, 65%). 1H NMR (500 MHz, CDCl3) δ 8.36 (s, 1H), 7.51 (s, 1H), 7.12 (d, J=4.8 Hz, 1H), 5.63 (s, 1H), 5.43 (s, 1H), 4.91 (d, J=6.3 Hz, 2H), 4.36 (d, J=6.8 Hz, 2H), 3.66 (s, 1H), 2.73 (s, 3H), 2.47 (s, 3H), 2.33 (m, 4H), 2.03 (m, 1H), 1.06 (s, 9H); LRMS (ES) calculated M+H for C23H31N6O2S: 455.6. Found:455.2.

Workup

  1. customThe excess TFA was removed under reduced pressure
  2. dissolutionThe residue was dissolved in dichloromethane (10 mL)
  3. extractionThe mixture was extracted with EtOAc
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. custompurified by reverse phase column (Waters Sunfire Prep C18 OBD, 5-95% methanol in water with 0.1% NH3H2O modifier)

Sources & evidence

ORD record
ord-f020df29e1b14ce6a9d5beeabd10a88a
Source dataset
uspto-grants-2015_06
Patent number
US09062059B2

Reaction notes

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