Hydrochloric Acid → HCID 56656336, compound

HRID 1431163Notes

Reaction equation

HRID 1431163 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]3[CH:28]=[C:27]([NH:29][C:30]4[CH:35]=[N:34][C:33]([C@H:36]5[CH2:40][O:39]C(C)(C)[O:37]5)=[CH:32][N:31]=4)[C:26](=[O:43])[N:25]([CH3:44])[N:24]=3)[C:18]=1[CH2:45][OH:46])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].Cl.[Cl-].[NH4+]>O1CCCC1>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]3[CH:28]=[C:27]([NH:29][C:30]4[CH:35]=[N:34][C:33]([C@H:36]([OH:37])[CH2:40][OH:39])=[CH:32][N:31]=4)[C:26](=[O:43])[N:25]([CH3:44])[N:24]=3)[C:18]=1[CH2:45][OH:46])[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 66742621HCID 66742621, compound

Product 1

HCID 56656336HCID 56656336, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-6-tert-butyl-2-(3-(5-(5-(2,2-dimethyl-1,3-dioxolan-4-yl)pyrazin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-2-(hydroxymethyl)phenyl)-8-fluorophthalazin-1(2H)-one (99 mg, 0.16 mmol) in tetrahydrofuran (4 mL) was added hydrochloric acid (1.0 N, 4 mL) and the resulting mixture stirred at room temperature overnight. The reaction mixture was poured into a saturated ammonium chloride solution and extracted with dichloromethane (2×50 mL). The combined organic layers were dried over magnesium sulfate. The mixture was filtered and evaporated and the residue recrystallized from dichloromethane and isopropyl acetate to give 6-tert-butyl-2-(3-{5-[5-((S)-1,2-dihydroxy-ethyl)-pyrazin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl}-2-hydroxymethyl-phenyl)-8-fluoro-2H-phthalazin-1-one (15.4 mg, 17%) as an off white solid: Mp. 218-224° C.; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.37 (s, 10H) 3.44-3.95 (m, 5H) 4.32-4.82 (m, 4H) 5.40 (d, J=4.91 Hz, 1H) 7.22-7.99 (m, 5H) 8.16-8.65 (m, 3H) 8.78 (s, 1H) 9.81 (s, 1H).

Workup

  1. extractionextracted with dichloromethane (2×50 mL)
  2. dry with materialThe combined organic layers were dried over magnesium sulfate
  3. filtrationThe mixture was filtered
  4. customevaporated
  5. customthe residue recrystallized from dichloromethane and isopropyl acetate

Sources & evidence

ORD record
ord-7146568c00064f3393f8884dc0e40c30
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

Loading…