Hydrochloric Acid → HCID 67416743, compound

HRID 2192985Notes

Reaction equation

HRID 2192985 reaction equation
[CH:1]1([C:4]#[C:5][C:6]2[C:15]3[N:14]=[C:13]([NH:16][C@@H:17]4[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][C@H:18]4[F:30])[C:12]4[CH:31]=[CH:32][C:33]([F:35])=[CH:34][C:11]=4[C:10]=3[C:9](=[O:36])[NH:8][CH:7]=2)[CH2:3][CH2:2]1.Cl.C(Cl)(Cl)Cl.C([O-])(O)=O.[Na+]>C1COCC1.CC(O)C>[CH:1]1([C:4]#[C:5][C:6]2[C:15]3[N:14]=[C:13]([NH:16][C@@H:17]4[CH2:22][CH2:21][NH:20][CH2:19][C@H:18]4[F:30])[C:12]4[CH:31]=[CH:32][C:33]([F:35])=[CH:34][C:11]=4[C:10]=3[C:9](=[O:36])[NH:8][CH:7]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6212ChloroformHCID 516892Sodium BicarbonateHCID 67417174HCID 67417174, compound

Product 1

HCID 67416743HCID 67416743, compound

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl trans-4-{[4-(cyclopropylethynyl)-9-fluoro-1-oxo-1,2-dihydrobenzo[c]-1,6-naphthyridin-6-yl]amino}-3-fluoropiperidine-1-carboxylate (160 mg, 0.324 mmol) in THF (5 mL) under a nitrogen atmosphere was added HCl (4.0 M in 1,4-dioxane) (2 mL, 8.0 mmol), and the reaction was left stirring for two days at room temperature. The reaction mixture was then added to a separatory funnel containing 3:1 CHCl3:2-propanol and saturated aqueous NaHCO3. The phases were separated, and the organic layer was washed with water, then brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product mixture was purified by silica gel chromatography (0-10% CH3OH in CH2Cl2), followed by trituration with methanol afforded the title compound 4-(cyclopropylethynyl)-9-fluoro-6-[(trans-3-fluoropiperidin-4-yl)amino]benzo[c]-1,6-naphthyridin-1(2H)-one. LRMS (APCI) calc'd (C22H20F2N4O3) [M+H]+, 395.2; found 395.1. 1H NMR (500 MHz, DMSO-d6) δ 11.51 (d, 1H), 9.57 (dd, 1H), 8.51 (dd, 1H), 8.19 (d, 1H), 7.57 (d, 1H), 7.53 (dt, 1H), 4.80-4.64 (m, 2H), 3.35 (m [under H2O], 1H), 2.97 (d, 1H), 2.55 (t, 2H), 2.12 (m, 1H), 1.56 (m, 1H), 1.50 (m, 1H), 1.15 (m, 1H), 0.89 (m, 2H), 0.72 (m, 2H).

Workup

  1. waitthe reaction was left
  2. additionThe reaction mixture was then added to a separatory funnel
  3. customThe phases were separated
  4. washthe organic layer was washed with water
  5. dry with materialbrine, dried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude product mixture was purified by silica gel chromatography (0-10% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-03f7c268c0684e78a0f996b3a79aa994
Source dataset
uspto-grants-2012_12
Patent number
US08329722B2

Reaction notes

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