Water → (S)-tert-butyl (1-(4-amino-5-(quinolin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)but-3-en-2-yl)carbamate

HRID 336161Notes

Reaction equation

HRID 336161 reaction equation
[NH2:1][C:2]1[C:3]2[C:10](I)=[CH:9][N:8]([CH2:12][C@@H:13]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH:14]=[CH2:15])[C:4]=2[N:5]=[CH:6][N:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CO[CH2:32][CH2:33]OC.O.C(O[CH2:41][CH3:42])(=O)C>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[NH2:1][C:2]1[C:3]2[C:10]([C:10]3[CH:9]=[N:8][C:4]4[C:32]([CH:33]=3)=[CH:42][CH:41]=[CH:2][CH:3]=4)=[CH:9][N:8]([CH2:12][C@@H:13]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH:14]=[CH2:15])[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

7

Reactant 5

HCID 962Water2×HCID 80711,2-DimethoxyethaneHCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 86711293HCID 86711293, compound

Product 1

HCID 86711294(S)-tert-butyl (1-(4-amino-5-(quinolin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)but-3-en-2-yl)carbamate

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
100 °C

Procedure

A mixture of (S)-tert-butyl (1-(4-amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)but-3-en-2-yl)carbamate (8.26 g) obtained in Step 2,3-quinolineboronic acid (4.99 g), cesium carbonate (12.54 g), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride (785.6 mg), DME (66 ml), and water (33 ml) was stirred under a nitrogen atmosphere at 100° C. for 2 hours. After cooling the reaction mixture, water and ethyl acetate were added thereto to separate the organic layer. The aqueous layer was then extracted with ethyl acetate twice. The resulting organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate, ethyl acetate/methanol) to obtain the title compound (8.0 g) as a light-orange solid.

Workup

  1. additionwere added
  2. customto separate the organic layer
  3. extractionThe aqueous layer was then extracted with ethyl acetate twice
  4. dry with materialThe resulting organic layer was dried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate, ethyl acetate/methanol)

Sources & evidence

ORD record
ord-e256dd50faa34f708c6c8561af5f2490
Source dataset
uspto-grants-2014_11
Patent number
US08889666B2

Reaction notes

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