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

HRID 510331Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 510331
[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]

Komponenten

8

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittel2×HCID 6344DichloromethaneLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

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.

Aufarbeitung

  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))

Quellen und Nachweise

ORD-Eintrag
ord-698796c92d654e0492a964d7a10ffc20
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09096604B2

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