Trifluoroacetic acid → HCID 58293600, compound

HRID 657577Notes

Reaction equation

HRID 657577 reaction equation
[CH3:1][C:2]1[C:7]([O:8][C:9]2[C:10]3[CH:18]=[CH:17][C:16](=[O:19])[N:15]([CH:20]4[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29](C)([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]4)[C:11]=3[N:12]=[CH:13][N:14]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.FC(F)(F)C(O)=O.C(N(CC)CC)C.C(OC(Cl)=O)(C)C>C(Cl)Cl.C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:1][C:2]1[C:7]([O:8][C:9]2[C:10]3[CH:18]=[CH:17][C:16](=[O:19])[N:15]([CH:20]4[CH2:21][CH2:22][N:23]([C:26]([O:28][CH:29]([CH3:31])[CH3:30])=[O:27])[CH2:24][CH2:25]4)[C:11]=3[N:12]=[CH:13][N:14]=2)=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7917Isopropyl chloroformateHCID 8471TriethylamineHCID 58293610HCID 58293610, compound

Product 1

HCID 58293600HCID 58293600, compound

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl 4-(4-(2-methylpyridin-3-yloxy)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)piperidine-1-carboxylate from Example 116C (56 mg, 0.13 mmol) in 4 mL methylene chloride was added 4 mL of trifluoroacetic acid. The resulting mixture was stirred at room temperature for 1 h and then was concentrated in vacuo. The residue was taken up in 4 mL of methylene chloride and then there was added triethylamine (0.054 mL, 0.38 mmol) and isopropylchloroformate (0.13 mL of a 1M solution in toluene, 0.13 mmol). The resulting mixture was allowed to stir at room temperature for 18 h. The reaction was diluted with ethyl acetate, washed with sat'd aq sodium bicarbonate and brine, dried (MgSO4), filtered through a pad of silica gel and concentrated. The residue was purified by silica gel chromatography (12 g ISCO cartridge, 0-100% ethyl acetate/hexane) to afford 28 mg (49%) of Example L16 as an off-white solid. 1H NMR (500 MHz, CDCl3) δ ppm 1.21 (d, J=6.05 Hz, 6 H) 1.55-1.61 (m, 2 H) 2.37 (s, 3 H) 2.80-2.93 (m, 4 H) 4.20-4.36 (m, 2 H) 4.85-4.92 (m, 1 H) 5.57 (s, 1 Ft) 6.70 (d, J=9.35 Hz, 1 H) 7.21 (dd, J=7.97, 4.67 Hz, 1 H) 7.40 (d, J=6.60 Hz, 1 H) 8.02 (d, J=9.35 Hz, 1 H) 8.42 (d, J=4.95 Hz, 1 H) 8.46 (s, 1 H). LRMS (ESI): 424.3 [M+H]+.

Workup

  1. concentrationwas concentrated in vacuo
  2. stirringto stir at room temperature for 18 h
  3. washwashed with sat'd aq sodium bicarbonate and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered through a pad of silica gel
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography (12 g ISCO cartridge, 0-100% ethyl acetate/hexane)
  8. customto afford 28 mg (49%) of Example L16 as an off-white solid

Sources & evidence

ORD record
ord-b16f87746ad440bba991f632fe25824c
Source dataset
uspto-grants-2011_12
Patent number
US08076322B2

Reaction notes

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