Trifluoroacetic acid → {6-[(6-Methoxy-pyridin-3-ylmethyl)-amino]-2-methyl-pyridin-3-yl}-(7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methanone

HRID 1403289Notes

Reaction equation

HRID 1403289 reaction equation
C(OC(=O)[N:7]([C:17]1[CH:22]=[CH:21][C:20]([CH:23]([OH:43])[C:24]2[C:32]3[CH:31]=[N:30][CH:29]=[N:28][C:27]=3[N:26]([Si](C(C)C)(C(C)C)C(C)C)[CH:25]=2)=[C:19]([CH3:44])[N:18]=1)[CH2:8][C:9]1[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=1)(C)(C)C.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCCl>[CH3:16][O:15][C:12]1[N:11]=[CH:10][C:9]([CH2:8][NH:7][C:17]2[N:18]=[C:19]([CH3:44])[C:20]([C:23]([C:24]3[C:32]4[CH:31]=[N:30][CH:29]=[N:28][C:27]=4[NH:26][CH:25]=3)=[O:43])=[CH:21][CH:22]=2)=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 57963213{5-[hydroxy-(7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methyl]-6-methyl-pyridin-2-yl}-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester

Product 1

HCID 57963198{6-[(6-Methoxy-pyridin-3-ylmethyl)-amino]-2-methyl-pyridin-3-yl}-(7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methanoneYield 30.7%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
70 °C

Procedure

To {5-[hydroxy-(7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methyl]-6-methyl-pyridin-2-yl}-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester (75, 0.317 g, 0.501 mmol) dissolved in 15.0 mL of 1,2-dichloroethane, triethylsilane (1.00 mL, 6.26 mmol) was added, followed by trifluoroacetic acid (0.482 mL, 6.26 mmol). The reaction was stirred at 70° C. overnight, then concentrated under vacuum and combined with 1 N aqueous potassium carbonate and extracted with ethyl acetate. The organic layer was washed with brine, then dried with sodium sulfate, filtered and the filtrate adsorbed onto silica. This was purified by silica gel column chromatography eluting with 50-100% ethyl acetate in hexanes. Appropriate fractions were combined and the solvents removed under vacuum to provide the desired compound (P-0019, 57.5 mg). 1H NMR was consistent with the compound structure.

Workup

  1. concentrationconcentrated under vacuum
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. customThis was purified by silica gel column chromatography
  7. washeluting with 50-100% ethyl acetate in hexanes
  8. customthe solvents removed under vacuum

Sources & evidence

ORD record
ord-ed3fdd9fded54397af1316d7e0e02e68
Source dataset
uspto-grants-2014_12
Patent number
US08912204B2

Reaction notes

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