Hydrochloric Acid → N-(2-Fluoro-5-(6-oxo-5-(5-(2-oxopiperazin-1-yl)pyridin-2-ylamino)-1,6-dihydropyridazin-3-yl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide

HRID 1907812Notes

Reaction equation

HRID 1907812 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([NH:15][C:16]3[N:21]=[CH:20][C:19]([N:22]4[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][C:23]4=[O:35])=[CH:18][CH:17]=3)[C:11](=[O:14])[NH:12][N:13]=2)=[CH:4][C:3]=1[NH:36][C:37]([C:39]1[S:43][C:42]2[CH2:44][CH2:45][CH2:46][CH2:47][C:41]=2[CH:40]=1)=[O:38].CO.Cl.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([NH:15][C:16]3[CH:17]=[CH:18][C:19]([N:22]4[CH2:27][CH2:26][NH:25][CH2:24][C:23]4=[O:35])=[CH:20][N:21]=3)[C:11](=[O:14])[NH:12][N:13]=2)=[CH:4][C:3]=1[NH:36][C:37]([C:39]1[S:43][C:42]2[CH2:44][CH2:45][CH2:46][CH2:47][C:41]=2[CH:40]=1)=[O:38]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 11430Potassium CarbonateHCID 58539996tert-Butyl 4-(6-(6-(4-Fluoro-3-(4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamido)phenyl)-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)-3-oxopiperazine-1-carboxylate

Product 1

HCID 58540158N-(2-Fluoro-5-(6-oxo-5-(5-(2-oxopiperazin-1-yl)pyridin-2-ylamino)-1,6-dihydropyridazin-3-yl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamideYield 56%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A 10-mL single-neck round bottomed flask equipped with a magnetic stirrer was purged with nitrogen and charged with 2h (75 mg, 0.129 mmol), methanol (2 mL) and 4 M HCl in dioxane (2 mL) and the mixture stirred for 2 h. After this time, ethyl acetate (20 mL) and water (20 mL) were added. The pH was adjusted to 6.5 with aqueous 10% potassium carbonate. The aqueous layer was separated and extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with brine (20 mL) and dried over sodium sulfate. The drying agent was removed by filtration. The filtrate was concentrated under reduced pressure to a residue which was purified by column chromatography to afford a 56% yield of 21 (40 mg) as a white solid: mp 285-287° C.; 1H NMR (500 MHz, DMSO-d6) δ13.21 (s, 1H), 10.07 (s, 1H), 9.50 (s, 1H), 8.36 (d, 1H, J=2.5 Hz), 8.04 (dd, 1H, J=7.5, 2.0 Hz), 7.71 (s, 1H), 7.70 (m, 1H), 7.65 (m, 1H), 7.53 (d, 1H, =9.0 Hz), 7.41 (t, 1H, J=9.0 Hz), 3.63 (t, 2H, J=5.5 Hz), 3.42 (s, 2H), 3.04 (t, 2H, J=5.0 Hz), 2.78 (t, 2H, J=5.0 Hz), 2.62 (t, 2H, J=5.5 Hz), 1.78 (m, 4H); MS (ESI+) m/z 560.0 (M+H).

Workup

  1. customA 10-mL single-neck round bottomed flask equipped with a magnetic stirrer
  2. customwas purged with nitrogen
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate (2×25 mL)
  5. washThe combined organic layers were washed with brine (20 mL)
  6. dry with materialdried over sodium sulfate
  7. customThe drying agent was removed by filtration
  8. concentrationThe filtrate was concentrated under reduced pressure to a residue which
  9. customwas purified by column chromatography

Sources & evidence

ORD record
ord-0ea72364584c4c1f8e0a8be89a5ae66a
Source dataset
uspto-grants-2013_12
Patent number
US08598174B2

Reaction notes

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