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

HRID 1771522노트

반응식

HRID 1771522 반응식
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

참가 물질

5

반응물 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-methylmorpholine2회

생성물 1

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

시약·촉매·용매 1

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

실험 절차

(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%.

후처리

  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%

출처 및 근거

ORD 기록
ord-22319ed241304688b372bf530b286755
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09249129B2

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