Cesium carbonate → (S)-1-(4-(6-chloro-2-(3-methylmorpholino)pyrimidin-4-yl)phenyl)-3-ethylurea

HRID 1771522Notes

Reaction equation

HRID 1771522 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][C@@H:10]2[CH3:15])[N:3]=1.[CH2:16]([NH:18][C:19](=[O:36])[NH:20][C:21]1[CH:26]=[CH:25][C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][CH:22]=1)[CH3:17].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O>[Cl:8][C:6]1[N:5]=[C:4]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][C@@H:10]2[CH3:15])[N:3]=[C:2]([C:24]2[CH:23]=[CH:22][C:21]([NH:20][C:19]([NH:18][CH2:16][CH3:17])=[O:36])=[CH:26][CH:25]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 44119377N-Ethyl-N'-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 72942068(S)-4-(4,6-Dichloropyrimidin-2-yl)-3-methylmorpholine2×

Product 1

HCID 86691150(S)-1-(4-(6-chloro-2-(3-methylmorpholino)pyrimidin-4-yl)phenyl)-3-ethylurea

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

(S)-4-(4,6-dichloropyrimidin-2-yl)-3-methylmorpholine (Intermediate 1B) (992 mg, 4.0 mmol), 4-(3-ethylureido)phenyl boronic acid pinacol ester (1.05 g, 3.6 mmol), cesium carbonate (3.9 g, 12.0 mmol) and bis(diphenylphosphino)-ferrocenedichloropalladium(II)-DCM-complex (163 mg, 0.2 mmol) in dioxane/water (1:3, 2.4 mL) were irradiated in a Biotage microwave for 40 min at 110° C. The reaction mixture was concentrated in vacuo, the residue suspended in water (150 mL) and the pH adjusted from 10 to 7 with HCl (2M aq solution). EtOAc (150 mL) was added and aqueous layer removed. The organic layer was washed with brine (70 mL) and then concentrated in vacuo to leave a brown solid which was purified by flash chromatography (0-5% MeOH in DCM over 30 min) to yield an orange solid, 630 mg, 42%.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additionEtOAc (150 mL) was added
  3. customaqueous layer removed
  4. washThe organic layer was washed with brine (70 mL)
  5. concentrationconcentrated in vacuo
  6. customto leave a brown solid which
  7. customwas purified by flash chromatography (0-5% MeOH in DCM over 30 min)
  8. customto yield an orange solid, 630 mg, 42%

Sources & evidence

ORD record
ord-22319ed241304688b372bf530b286755
Source dataset
uspto-grants-2016_02
Patent number
US09249129B2

Reaction notes

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