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 2359364ノート

反応式

HRID 2359364 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-2de2cb49cbd844d595914538c2f8cfbc
出典データセット
uspto-grants-2014_04
特許番号
US08685988B2

反応ノート

読み込み中…