Sodium Carbonate → 4-{2-Amino-6-[(1,1-dimethyl-2-phenylethyl)amino]-4-pyrimidinyl}-2-fluorobenzonitrile

HRID 2367261노트

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HRID 2367261 반응식
Cl[C:2]1[N:7]=[C:6]([NH2:8])[N:5]=[C:4]([NH:9][C:10]([CH3:19])([CH3:18])[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:3]=1.[F:20][C:21]1[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:26]=[CH:25][C:22]=1[C:23]#[N:24].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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>[NH2:8][C:6]1[N:7]=[C:2]([C:27]2[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[C:21]([F:20])[CH:28]=2)[CH:3]=[C:4]([NH:9][C:10]([CH3:19])([CH3:18])[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:5]=1

참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 513509512-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrileHCID 866591756-Chloro-N4-(1,1-dimethyl-2-phenylethyl)-2,4-pyrimidinediamine

생성물 1

HCID 669915204-{2-Amino-6-[(1,1-dimethyl-2-phenylethyl)amino]-4-pyrimidinyl}-2-fluorobenzonitrile수율 47.6%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
140 °C

실험 절차

A mixture of 6-chloro-N4-(1,1-dimethyl-2-phenylethyl)-2,4-pyrimidinediamine (338 mg, 1.22 mmol), 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (452 mg, 1.83 mmol), Pd(PPh3)4 (139 mg, 0.12 mmol) and Na2CO3 (323 mg, 3.05 mmol) in 1,4-dioxane (6 mL) and water (2 mL) was stirred and heated at 140° C. for 30 min in a Biotage Initiator microwave synthesizer. The reaction mixture was cooled to room temperature and concentrated to dryness, and the resulting residue was partitioned between EtOAc and water. The aqueous layer was extracted by EtOAc (3×50 mL), and the combined organic layers were dried over Na2SO4, filtered and concentrated to dryness. Purification by RPHPLC with CH3CN in water (0.01% ammonium hydrogen carbonate) (gradient: from 70% to 80% in 7.5 min, flow rate: 30 mL/min), afforded the title compound (210 mg) as a white solid. LC-MS (ES) m/z=362 [M+H]+.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated to dryness
  3. customthe resulting residue was partitioned between EtOAc and water
  4. extractionThe aqueous layer was extracted by EtOAc (3×50 mL)
  5. dry with materialthe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customPurification by RPHPLC with CH3CN in water (0.01% ammonium hydrogen carbonate) (gradient: from 70% to 80% in 7.5 min, flow rate: 30 mL/min)

출처 및 근거

ORD 기록
ord-b19f1fa0431947c69a0440c287b82853
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08697685B2

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