Hydrochloric Acid → HCID 71511507, compound

HRID 1055144Notes

Reaction equation

HRID 1055144 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-6e788213467f42b888fdc4e3f5480b7d
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

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