Dimethyl Sulfoxide → Isopropyl 4-(6-(2,4-dimethyl-6-(methylsulfonyl)pyridin-3-ylamino)-5-methoxypyrimidin-4-yloxy)piperidine-1-carboxy-late

HRID 1811587Notes

Reaction equation

HRID 1811587 reaction equation
Br[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([NH:9][C:10]2[N:15]=[CH:14][N:13]=[C:12]([O:16][CH:17]3[CH2:22][CH2:21][N:20]([C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]3)[C:11]=2[O:29][CH3:30])=[C:4]([CH3:31])[CH:3]=1.[OH2:32].C[S:34]([CH3:36])=[O:35]>>[CH3:8][C:6]1[C:5]([NH:9][C:10]2[N:15]=[CH:14][N:13]=[C:12]([O:16][CH:17]3[CH2:22][CH2:21][N:20]([C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]3)[C:11]=2[O:29][CH3:30])=[C:4]([CH3:31])[CH:3]=[C:2]([S:34]([CH3:36])(=[O:32])=[O:35])[N:7]=1

Participants

4

Reactant 3

HCID 679Dimethyl SulfoxideHCID 962WaterHCID 58671560Isopropyl 4-(6-(6-bromo-2,4-dimethylpyridin-3-ylamino)-5-methoxypyrimidin-4-yloxy)piperidine-1-carboxylate

Product 1

HCID 11555004Isopropyl 4-(6-(2,4-dimethyl-6-(methylsulfonyl)pyridin-3-ylamino)-5-methoxypyrimidin-4-yloxy)piperidine-1-carboxy-late

Conditions

Temperature
150 °C

Procedure

To a solution of isopropyl 4-(6-(6-bromo-2,4-dimethylpyridin-3-ylamino)-5-methoxypyrimidin-4-yloxy)piperidine-1-carboxylate (500 mg, 1.0 mmol) in 10 ml of DMSO, were added sodium sulfinate (0.36 g, 3.5 mmol), (CuOTf)2PhH (0.051 g, 0.10 mmol), and N,N′-dimethylethylamine (0.018 g, 0.20 mmol) at an ambient temperature. The reaction was heated to 150° C. for 8 hrs. The reaction was cooled to room temperature and poured into H2O. The organics were extracted with ethyl acetate and dried over MgSO4. The ethyl acetate was concentrated under vacuum and purified over SiO2 to afford isopropyl 4-(6-(2,4-dimethyl-6-(methylsulfonyl)pyridin-3-ylamino)-5-methoxypyrimidin-4-yloxy)piperidine-1-carboxy-late. 1HNMR (CDCl3, 400 MHz) δ 1.24 (d, J=1.6 Hz, 6H), 1.75-1.81 (m, 2H), 1.98-2.02 (m, 2H), 2.25 (s, 3H), 2.65 (s, 3H), 3.21 (s, 3H), 3.52-3.65 (m, 2H), 3.65-3.75 (m, 1H), 3.84 (s, 3H), 5.21-5.35 (m, 1H), 7.78 (s, 1H), 7.79 (s, 1H), 8.89 (s, 1H). Exact mass calculated for C22H31N5O6S 493.58 found 494.5 (MH+).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. extractionThe organics were extracted with ethyl acetate
  3. dry with materialdried over MgSO4
  4. concentrationThe ethyl acetate was concentrated under vacuum
  5. custompurified over SiO2

Sources & evidence

ORD record
ord-9b1bb94234ea46f6ae4b7ebf54bce026
Source dataset
uspto-grants-2013_01
Patent number
US08362248B2

Reaction notes

Loading…