2-Chloro-4,6-dimethylpyrimidine → (1R,6S)-3-(4,6-Dimethylpyrimidin-2-yl)-8-{[2-fluoro-6-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-3,8-diazabicyclo[4.2.0]octane

HRID 2175045Notes

Reaction equation

HRID 2175045 reaction equation
[C@@H:1]12[N:8]([C:9]([C:11]3[C:16]([N:17]4[N:21]=[CH:20][CH:19]=[N:18]4)=[CH:15][CH:14]=[CH:13][C:12]=3[F:22])=[O:10])[CH2:7][C@@H:6]1[CH2:5][CH2:4][NH:3][CH2:2]2.Cl[C:24]1[N:29]=[C:28]([CH3:30])[CH:27]=[C:26]([CH3:31])[N:25]=1.CCN(C(C)C)C(C)C>C(#N)C.O>[CH3:31][C:26]1[CH:27]=[C:28]([CH3:30])[N:29]=[C:24]([N:3]2[CH2:4][CH2:5][C@@H:6]3[C@@H:1]([N:8]([C:9]([C:11]4[C:16]([N:17]5[N:18]=[CH:19][CH:20]=[N:21]5)=[CH:15][CH:14]=[CH:13][C:12]=4[F:22])=[O:10])[CH2:7]3)[CH2:2]2)[N:25]=1

Participants

6

Reactant 3

HCID 205502-Chloro-4,6-dimethylpyrimidineHCID 81531DiisopropylethylamineHCID 67086872(1R,6S)-3,8-Diazabicyclo[4.2.0]octan-8-yl(2-fluoro-6-(2H-1,2,3-triazol-2-yl)phenyl)methanone2×

Product 1

HCID 52915672(1R,6S)-3-(4,6-Dimethylpyrimidin-2-yl)-8-{[2-fluoro-6-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}-3,8-diazabicyclo[4.2.0]octaneYield 53%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

(1R,6S)-3,8-Diazabicyclo[4.2.0]octan-8-yl(2-fluoro-6-(2H-1,2,3-triazol-2-yl)phenyl)methanone (Intermediate 29, 56 mg, 0.19 mmol), 2-chloro-4,6-dimethylpyrimidine (32 mg, 0.22 mmol) and DIPEA (96 μL, 0.56 mmol) in ACN (2 mL) were heated in a microwave reactor for 1 h at 150° C. Then the reaction mixture was diluted with water and extracted with DCM (2×). The combined organics were dried (Na2SO4) and concentrated. Purification via prep HPLC (Agilent, basic) gave 40 mg (53%) of the title compound as a clear oil. MS (ESI) mass calcd. For C21H22FN7O, 407.45; m/z found 408.0 [M+H]+. 1H NMR (CDCl3): 8.00-6.88 (m, 5H), 6.38-5.88 (m, 1H), 4.95-3.57 (m, 6H), 3.29-2.61 (m, 2H), 2.47-1.80 (m, 8H).

Workup

  1. extractionextracted with DCM (2×)
  2. dry with materialThe combined organics were dried (Na2SO4)
  3. concentrationconcentrated
  4. customPurification via prep HPLC (Agilent, basic)

Sources & evidence

ORD record
ord-33f0db0f453b4ea59589e257f639ac5f
Source dataset
uspto-grants-2015_06
Patent number
US09062044B2

Reaction notes

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