Potassium Carbonate → (2-(4-(1-(2-fluoroethyl)azetidin-3-ylamino)-2-methoxyphenylamino)-4-(3-nitrophenoxy)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate

HRID 574277노트

반응식

HRID 574277 반응식
[F:1][CH2:2][CH2:3][N:4]1[CH2:7][CH:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[C:11]([O:16][CH3:17])[CH:10]=2)[CH2:5]1.[C:18]([O:24][CH2:25][N:26]1[C:30]2[N:31]=[C:32](Cl)[N:33]=[C:34]([O:35][C:36]3[CH:41]=[CH:40][CH:39]=[C:38]([N+:42]([O-:44])=[O:43])[CH:37]=3)[C:29]=2[CH:28]=[CH:27]1)(=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20].C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(O)(C)C>[C:18]([O:24][CH2:25][N:26]1[C:30]2[N:31]=[C:32]([NH:15][C:12]3[CH:13]=[CH:14][C:9]([NH:8][CH:6]4[CH2:7][N:4]([CH2:3][CH2:2][F:1])[CH2:5]4)=[CH:10][C:11]=3[O:16][CH3:17])[N:33]=[C:34]([O:35][C:36]3[CH:41]=[CH:40][CH:39]=[C:38]([N+:42]([O-:44])=[O:43])[CH:37]=3)[C:29]=2[CH:28]=[CH:27]1)(=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20]

참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86709973HCID 86709973, 화합물HCID 86709976(2-chloro-4-(3-nitrophenoxy)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate

생성물 1

HCID 86709975(2-(4-(1-(2-fluoroethyl)azetidin-3-ylamino)-2-methoxyphenylamino)-4-(3-nitrophenoxy)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate수율 76.9%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 6386tert-Butanol용매

반응 조건

온도
45 °C

실험 절차

A mixture of N1-(1-(2-fluoroethyl)azetidin-3-yl)-3-methoxybenzene-1,4-diamine (870 mg, 3.64 mmol) and (2-chloro-4-(3-nitrophenoxy)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate (1.55 g, 3.83 mmol), potassium carbonate (1.35 g, 9.77 mmol), tris(dibenzylideneacetone)dipalladium (173 mg, 0.19 mmol) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (222 mg, 0.47 mmol), a magnetite, and t-BuOH (35 mL) was heated to reflux and stirred under nitrogen for 2 h. The mixture was cooled to 40-50° C. and was filtered through diatomaceous earth, washing with ethyl acetate (50 mL). The filtrate was concentrated under reduced pressure. The crude material was purified by column chromatography (DCM/MeOH=50/1 as elution) to give the title compound (1.7 g, yield 74%, M+H+=608.3) as a light yellow solid.

후처리

  1. temperatureto reflux
  2. filtrationwas filtered through diatomaceous earth
  3. washwashing with ethyl acetate (50 mL)
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customThe crude material was purified by column chromatography (DCM/MeOH=50/1 as elution)

출처 및 근거

ORD 기록
ord-fb4d7aa28f0b49fcae336a11c7766969
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09034885B2

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