Water → tert-butyl N-[4-(4-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl]carbamate

HRID 251489Notes

Reaction equation

HRID 251489 reaction equation
O.[CH3:2][O:3][C:4]1[CH:9]=[C:8](B2OC(C)(C)C(C)(C)O2)[CH:7]=[CH:6][C:5]=1[NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23].[Cl:27][C:28]1[C:29]2[C:36](I)=[CH:35][N:34]([CH:38]3[CH2:42][CH2:41][CH2:40][CH2:39]3)[C:30]=2[N:31]=[CH:32][N:33]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC>[Cl:27][C:28]1[C:29]2[C:36]([C:8]3[CH:7]=[CH:6][C:5]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[C:4]([O:3][CH3:2])[CH:9]=3)=[CH:35][N:34]([CH:38]3[CH2:42][CH2:41][CH2:40][CH2:39]3)[C:30]=2[N:31]=[CH:32][N:33]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 177502214-(tert-Butoxycarbonylamino)-3-methoxyphenylboronic acid, pinacol esterHCID 195974344-Chloro-7-cyclopentyl-5-iodo-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 53777291tert-butyl N-[4-(4-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl]carbamateYield 81.3%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of water (25 ml) and tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (65% pure) (4.25 g, 7.92 mmol) was frozen and subjected to vacuum followed by filling with nitrogen while defreezing. 4-Chloro-7-cyclopentyl-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (1.83 g, 5.28 mmol), tetrakis (triphenylphosphine)palladium(0) (0.37 g, 0.32 mmol), sodium carbonate (1.40 g, 13.20 mmol) and ethylene glycol dimethyl ether (50 ml) were added and the resulting mixture was heated at 80° C. under an atmosphere of nitrogen overnight. The mixture was allowed to cool to ambient temperature and the solvent was removed under reduced pressure to give a residue which was partitioned between water and ethyl acetate. The organic layer was separated and the aqueous layer was further extracted with ethyl acetate twice. The combined ethyl acetate extracts were dried over magnesium sulfate and evaporated to give a dark oil which was purified by flash column chromatography on silica using n-heptane/ethyl acetate (3:1) with 2% triethylamine as the mobile phase. Appropriate fractions were collected, combined and concentrated to give tert-butyl N-[4-(4-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl]carbamate as white solids (1.90 g, 4.29 mmol): 1H NMR (DMSO-d6, 400 MHz) δ 8.65 (s, 1H), 7.94 (s, 2H), 7.74 (d, 1H), 7.19 (d, 1H), 7.07 (dd, 1H), 5.22 (m, 1H), 3.87 (s, 3H), 2.19 (m, 2H), 1.99 (m, 2H), 1.91 (m, 2H), 1.73 (m, 2H), 1.48 (s, 9H); TLC (n-heptane/ethyl acetate=1:1) Rf 0.58.

Workup

  1. temperaturewas frozen
  2. temperatureto cool to ambient temperature
  3. customthe solvent was removed under reduced pressure
  4. customto give a residue which
  5. customwas partitioned between water and ethyl acetate
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was further extracted with ethyl acetate twice
  8. dry with materialThe combined ethyl acetate extracts were dried over magnesium sulfate
  9. customevaporated
  10. customto give a dark oil which
  11. customwas purified by flash column chromatography on silica
  12. customAppropriate fractions were collected
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-a42d4f6a7f00429397523b919b73cd27
Source dataset
uspto-grants-2011_01
Patent number
US07863444B2

Reaction notes

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