Potassium Carbonate → Methyl 1-(2-(5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)-2-fluorophenoxy)ethyl)piperidine-4-carboxylate

HRID 2067909

반응식

HRID 2067909 반응식
Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([F:28])=[C:13]([CH:27]=2)[O:14][CH2:15][CH2:16][N:17]2[CH2:22][CH2:21][CH:20]([C:23]([O:25][CH3:26])=[O:24])[CH2:19][CH2:18]2)=[N:6][CH:7]=1.[F:29][CH:30]([F:47])[O:31][C:32]1[CH:37]=[CH:36][C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][CH:33]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:29][CH:30]([F:47])[O:31][C:32]1[CH:37]=[CH:36][C:35]([C:2]2[CH:3]=[N:4][C:5]([NH:8][C:9]3[CH:10]=[CH:11][C:12]([F:28])=[C:13]([CH:27]=3)[O:14][CH2:15][CH2:16][N:17]3[CH2:22][CH2:21][CH:20]([C:23]([O:25][CH3:26])=[O:24])[CH2:19][CH2:18]3)=[N:6][CH:7]=2)=[CH:34][CH:33]=1

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 220323032-(4-(Difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 58542307Methyl 1-(2-(5-(5-bromopyrimidin-2-ylamino)-2-fluorophenoxy)ethyl)piperidine-4-carboxylate

생성물 1

HCID 68729011Methyl 1-(2-(5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)-2-fluorophenoxy)ethyl)piperidine-4-carboxylate

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 312751,4-Dioxane용매

반응 조건

온도
90 °C

실험 절차

To a solution of methyl 1-(2-(5-(5-bromopyrimidin-2-ylamino)-2-fluorophenoxy)ethyl)piperidine-4-carboxylate 47 (0.24 mmol) in 1,4-dioxane (2.0 mL) is added 2-(4-(difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 7 (0.28 mmol), 1.8M K2CO3 (0.5 mmol) and Pd(PPh3)4 (0.017 mmol). The reaction is evacuated and backfilled with nitrogen twice then heated at 90° C. for 12 h. The reaction mixture is cooled to rt, diluted with water (10 mL) and extracted with DCM (2×20 mL). The organic layer is separated, dried over Na2SO4 and concentrated. Purification by preparative HPLC (ACN gradient 20-70%) affords methyl 1-(2-(5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)-2-fluorophenoxy)ethyl)piperidine-4-carboxylate 48 as white solid. MS (m/z) (M+1)+: 517.1.

후처리

  1. customThe reaction is evacuated
  2. temperatureThe reaction mixture is cooled to rt
  3. additiondiluted with water (10 mL)
  4. extractionextracted with DCM (2×20 mL)
  5. customThe organic layer is separated
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customPurification by preparative HPLC (ACN gradient 20-70%)

출처 및 근거

ORD 기록
ord-450acc2f32a1490b905f8b41bdab7030
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08293757B2

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