Cesium carbonate → 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

HRID 2175424Notes

Reaction equation

HRID 2175424 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[CH:23]=[C:22](Cl)[N:21]=[C:20]([CH3:25])[N:19]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:26][C:27]1[S:31][C:30]([CH2:32][NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[N:29][N:28]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[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:19]=[C:20]([CH3:25])[N:21]=[C:22]([N:33]([CH2:32][C:30]2[S:31][C:27]([CH3:26])=[N:28][N:29]=2)[C:34](=[O:40])[O:35][C:36]([CH3:37])([CH3:38])[CH3:39])[CH:23]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 59892191Tert-butyl ((5-methyl-1,3,4-thiadiazol-2-yl)methyl)carbamateHCID 867295764-((2-Tert-butoxy-3-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-6-chloro-2-methylpyrimidine

Product 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)carbamateYield 49%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

The mixture of 12-6 (160 mg, 0.4421 mmol), tert-butyl (5-methyl-1,3,4-thiadiazol-2-yl)methylcarbamate (122 mg, 0.53 mmol), BINAP (31 mg, 0.049 mmol) and cesium carbonate (173 mg, 0.53 mmol) in toluene (2 mL) was stirred for 5 min before Pd(OAc)2 (10 mg, 0.044 mmol) was added. The mixture was degassed with nitrogen for 5 min, then it was heated to 80° C. for overnight. The solvent was removed under reduced pressure and the residue was purified by Pre-TLC (PE/EA=1/1). The product was obtained as a white solid (120 mg, 49%). 1H NMR (400 MHz, CDCl3) δ 8.34 (s, 1H), 7.39 (d, J=7.9 Hz, 1H), 7.17 (s, 1H), 7.03 (d, J=8.1 Hz, 1H), 5.52 (s, 2H), 4.52-4.18 (m, 2H), 3.64 (dd, J=6.8, 3.6 Hz, 1H), 2.73 (s, 1H), 2.69 (s, 3H), 2.52 (s, 3H), 2.30 (s, 3H), 2.27 (m, 1H), 2.04 (m, 1H), 1.50 (s, 9H), 1.07 (s, 9H); LRMS (ES) calculated M+H for C28H39N6O4S: 555.7. Found: 555.1.

Workup

  1. additionwas added
  2. customThe mixture was degassed with nitrogen for 5 min
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified by Pre-TLC (PE/EA=1/1)

Sources & evidence

ORD record
ord-604d5a1207824dadaed48c3aae5fef57
Source dataset
uspto-grants-2015_06
Patent number
US09062059B2

Reaction notes

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