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 574277ノート

反応式

HRID 574277 の反応式
[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]

参加物

7

反応物 4

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

生成物 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 pivalate収率 76.9%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 6386tert-Butanol溶媒

反応条件

温度
45 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-fb4d7aa28f0b49fcae336a11c7766969
出典データセット
uspto-grants-2015_05
特許番号
US09034885B2

反応ノート

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