2-Chloropyrimidine → HCID 67608326, compound

HRID 1965219Notes

Reaction equation

HRID 1965219 reaction equation
[C:1]([O:5][C:6](=[O:39])[N:7]([CH:9]([C:11](=[O:38])[NH:12][CH:13]([C:18]([N:20]1[CH2:24][CH2:23][CH:22]2[NH:25][CH2:26][CH:27]([CH2:28][O:29][C:30]3[CH:35]=[CH:34][C:33]([F:36])=[C:32]([F:37])[CH:31]=3)[CH:21]12)=[O:19])[C:14]([CH3:17])([CH3:16])[CH3:15])[CH3:10])[CH3:8])([CH3:4])([CH3:3])[CH3:2].Cl[C:41]1[N:46]=[CH:45][CH:44]=[CH:43][N:42]=1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[C:1]([O:5][C:6](=[O:39])[N:7]([CH:9]([C:11](=[O:38])[NH:12][CH:13]([C:18]([N:20]1[CH2:24][CH2:23][CH:22]2[N:25]([C:41]3[N:46]=[CH:45][CH:44]=[CH:43][N:42]=3)[CH2:26][CH:27]([CH2:28][O:29][C:30]3[CH:35]=[CH:34][C:33]([F:36])=[C:32]([F:37])[CH:31]=3)[CH:21]12)=[O:19])[C:14]([CH3:16])([CH3:17])[CH3:15])[CH3:10])[CH3:8])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 744042-ChloropyrimidineHCID 81531DiisopropylethylamineHCID 67606764HCID 67606764, compound

Product 1

HCID 67608326HCID 67608326, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of amine 84 (325 mg, 0.59 mmol) in DMF (8 mL) was treated with 2-chloropyrimidine (88 mg, 0.76 mmol) and DIPEA (0.15 mL, 0.88 mmol) and heated to 80° C. in an oil bath. After 18 h, the reaction mixture was cooled to ambient temperature, diluted with water, and extracted with Et2O (3×). The combined organic extracts were washed successively with water (3×), and brine, dried over anhydrous Na2SO4, filtered and concentrated to afford 89 (341 mg, 92%) as an orange-colored solid that was used without further purification. 1H NMR (CDCl3, 300 MHz): δ8.67 (d, J=4.8 Hz, 1H), 8.35 (d, J=5.1 Hz, 1H), 7.30 (t, J=4.8 Hz, 1H), 7.08-6.87 (m, 1H), 6.86 (br s, 1H), 6.79-6.72 (m, 1H), 6.67-6.49 (m, 2H), 4.74-4.53 (m, 3H), 4.40-4.36 (m, 0.5H), 4.19-4.17 (m, 0.5H), 4.08-3.93 (m, 3H), 3.86-3.80 (m, 1H), 3.68-3.54 (m, 1H), 3.49-3.99 (m, 1H), 3.27-2.89 (m, 2H), 2.79 (s, 3H), 2.48-2.44 (m, 1.5H), 2.21-2.11 (m, 0.5H), 2.01-1.84 (m, 2H), 1.50-1.48 (m, 9H), 1.34-1.30 (m, 3H), 1.03-0.95 (m, 9H) ppm.

Workup

  1. temperaturethe reaction mixture was cooled to ambient temperature
  2. extractionextracted with Et2O (3×)
  3. washThe combined organic extracts were washed successively with water (3×), and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-607a958f354748e3a6f53a7426ae91b8
Source dataset
uspto-grants-2013_04
Patent number
US08415486B2

Reaction notes

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