Hydrochloric Acid → HCID 71511507, compound

HRID 2171940Notes

Reaction equation

HRID 2171940 reaction equation
[F:1][C:2]1[C:3]([NH:28][CH:29]([C:36]2([CH3:42])[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)[CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[N:10](S(C3C=CC(C)=CC=3)(=O)=O)[CH:9]=2)=[N:6][CH:7]=1.Cl>CC#N>[F:1][C:2]1[C:3]([NH:28][CH:29]([C:36]2([CH3:42])[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)[CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[NH:10][CH:9]=2)=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 71251342HCID 71251342, compound2×

Product 1

HCID 71511507HCID 71511507, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of ethyl 3-(5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4ylamino)-3-(1-methylcyclohexyl)propanoate, 207a, (0.49 mg, 0.81 mmol) in CH3CN (3 mL) was added HCl (2.0 mL of 4M solution in dioxane, 8.1 mmol). The solution was heated at 70° C. for 3 hours and then cooled to room temperature. The solvent was removed under reduced pressure and the product was neutralized with aqueous saturated NaHCO3 solution. The precipitate was extracted with EtOAc (3×10 mL). The solvent was dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography (0-70% EtOAc/Hexanes gradient) to afford 230 mg of the desired product as an off-white solid: 1H NMR (400 MHz, CDCl3) δ 9.55 (s, 1H), 8.58 (dd, J=9.3, 2.5 Hz, 1H), 8.18 (s, 2H), 8.00 (d, J=2.7 Hz, 1H), 5.13 (brs, 1H), 4.95 (t, J=8.2 Hz, 1H), 3.84 (m, 2H), 2.72 (m, 1H), 2.38 (m, 1H), 1.67-1.15 (m, 10H), 0.94 (m, 3H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=2.77 minutes (M+H) 444.36.

Workup

  1. temperaturecooled to room temperature
  2. customThe solvent was removed under reduced pressure
  3. extractionThe precipitate was extracted with EtOAc (3×10 mL)
  4. dry with materialThe solvent was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified by silica gel chromatography (0-70% EtOAc/Hexanes gradient)

Sources & evidence

ORD record
ord-a8f8de1f64634af78637c77ca1be4bf7
Source dataset
uspto-grants-2015_06
Patent number
US09051319B2

Reaction notes

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