Sodium Carbonate → (R)-tert-butyl-3-(4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate

HRID 510331노트

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HRID 510331 반응식
[NH2:1][C:2]1[C:3]2[C:10](I)=[CH:9][N:8]([C@@H:12]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[O:24]([C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.O.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:20]([O:19][C:17]([N:14]1[CH2:15][CH2:16][C@@H:12]([N:8]2[C:4]3[N:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=3[C:10]([C:34]3[CH:35]=[CH:36][C:31]([O:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[CH:32][CH:33]=3)=[CH:9]2)[CH2:13]1)=[O:18])([CH3:23])([CH3:22])[CH3:21]

참가 물질

8

반응물 3

HCID 10340Sodium CarbonateHCID 27343774-Phenoxyphenylboronic acidHCID 67035017(R)-tert-butyl 3-(4-amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate

생성물 1

HCID 86719376(R)-tert-butyl-3-(4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate수율 60%

시약·촉매·용매 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매2회HCID 6344Dichloromethane용매HCID 80711,2-Dimethoxyethane용매

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온도
90 °C

실험 절차

A mixture of (R)-tert-butyl 3-(4-amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (1) (2.0 g, 4.66 mmol), 4-phenoxyphenylboronic acid (1.3 g, 6.06 mmol), Pd(dppf)Cl2 (190 mg, 0.23 mmol) and Na2CO3 (1.9 g, 14.0 mmol) in DME (35.0 mL) and H2O (15.0 mL) was heated at 90° C. under N2 atmosphere overnight. After cooled down to r. t., the reaction mixture was diluted with water (50.0 mL) and DCM (50.0 mL). The layers were separated and the aqueous phase was extracted with DCM (25 mL×1). Combined organic phases were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to obtain the crude product which was purified by column chromatographic (silica gel, 0-80% ethyl acetate in petroleum ether (“PE”) with DCM (1:1)) to afford (R)-tert-butyl-3-(4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (2) (1.3 g, 60% yield) as a yellow solid. LC-MS (ESI): (M+1) 472.1.

후처리

  1. temperatureAfter cooled down to r
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted with DCM (25 mL×1)
  4. washCombined organic phases were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customto obtain the crude product which
  8. customwas purified by column chromatographic (silica gel, 0-80% ethyl acetate in petroleum ether (“PE”) with DCM (1:1))

출처 및 근거

ORD 기록
ord-698796c92d654e0492a964d7a10ffc20
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096604B2

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