Water → HCID 67442898, compound

HRID 1396181Notes

Reaction equation

HRID 1396181 reaction equation
C(OC(=O)[N:7]([C:39]1[CH:40]=[N:41][C:42](Cl)=[CH:43][CH:44]=1)[C:8]1[CH:13]=[CH:12][C:11]([CH:14]([C:16]2[C:24]3[C:23]([CH:25]4[CH2:27][CH2:26]4)=[N:22][CH:21]=[N:20][C:19]=3[N:18]([Si:28]([CH:35]([CH3:37])[CH3:36])([CH:32]([CH3:34])[CH3:33])[CH:29]([CH3:31])[CH3:30])[CH:17]=2)[OH:15])=[C:10]([F:38])[N:9]=1)(C)(C)C.[CH:47]1([Mg]Br)[CH2:49][CH2:48]1.O>C1(C)C=CC=CC=1.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]>[CH:47]1([C:42]2[N:41]=[CH:40][C:39]([NH:7][C:8]3[N:9]=[C:10]([F:38])[C:11]([CH:14]([C:16]4[C:24]5[C:23]([CH:25]6[CH2:26][CH2:27]6)=[N:22][CH:21]=[N:20][C:19]=5[N:18]([Si:28]([CH:32]([CH3:33])[CH3:34])([CH:35]([CH3:36])[CH3:37])[CH:29]([CH3:31])[CH3:30])[CH:17]=4)[OH:15])=[CH:12][CH:13]=3)=[CH:44][CH:43]=2)[CH2:49][CH2:48]1

Participants

6

Reactant 3

HCID 962WaterHCID 58485758HCID 58485758, compoundHCID 178418630HCID 178418630, compound

Product 1

HCID 67442898HCID 67442898, compoundYield 90.7%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
65 °C

Procedure

To (6-chloro-pyridin-3-yl)-{5-[(4-cyclopropyl-7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-hydroxy-methyl]-6-fluoro-pyridin-2-yl}-carbamic acid tert-butyl ester (81, 0.51 g, 0.77 mmol) in 12 mL of toluene, [1,1′-bis(diphenylphosphino) ferrocene]dichloropalladium(II) (0.13 g, 0.17 mmol) is added under nitrogen and the reaction stirred for 5 minutes. Cyclopropylmagnesium bromide (17, 15.29 mL, 0.50 M in tetrahydrofuran, 7.65 mmol) is added slowly and the reaction is heated at 65° C. for 2 hours. The reaction is poured into water and extracted with ethyl acetate. The organic layer is dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with 20-100% ethyl acetate in hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (82, 400 mg).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer is dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated under vacuum
  5. customThe resulting material is purified by silica gel column chromatography
  6. washeluting with 20-100% ethyl acetate in hexane
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-c71a59816c6842d199eeae3a81eeccdf
Source dataset
uspto-grants-2014_12
Patent number
US08901118B2

Reaction notes

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