Hydrochloric Acid → HCID 56656453, compound

HRID 449712Notes

Reaction equation

HRID 449712 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:34]=[CH:33][N:32]([CH2:35][C@@H:36]5[CH2:40][O:39]C(C)(C)[O:37]5)[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:34]=[CH:33][N:32]([CH2:35][C@@H:36]([OH:37])[CH2:40][OH:39])[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 66742482HCID 66742482, compound

Product 1

HCID 56656453HCID 56656453, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-6-tert-butyl-2-(3-(5-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-2-(hydroxymethyl)phenyl)-8-fluorophthalazin-1(2H)-one (135 mg, 0.21 mmol) in tetrahydrofuran (4 ml) was added a solution of hydrochloric acid (1.0 N, 4 ml) and the resulting solution was stirred at room temperature overnight. The resulting mixture was poured into a saturated aqueous ammonium chloride solution and extracted with dichloromethane (2×50 mL). The organic layers were combined and dried over magnesium sulfate. The mixture was filtered and evaporated and the residue crystallized from dichloromethane and isopropyl acetate. The crystals were washed with ether and dried to give 6-tert-butyl-2-(3-{5-[1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl}-2-hydroxymethyl-phenyl)-8-fluoro-2H-phthalazin-1-one (52 mg, 41%) as a light yellow solid: mp. 245-250° C.; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.38 (s, 9H) 3.67-4.24 (m, 6H) 4.27-5.06 (m, 5H) 6.19 (d, J=2.27 Hz, 1H) 7.18-7.96 (m, 7H) 8.51 (d, J=2.27 Hz, 1H) 9.23 (s, 1H).

Workup

  1. extractionextracted with dichloromethane (2×50 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationThe mixture was filtered
  4. customevaporated
  5. customthe residue crystallized from dichloromethane and isopropyl acetate
  6. washThe crystals were washed with ether
  7. customdried

Sources & evidence

ORD record
ord-7d216c6be1e846648a6da6a56bb35cf3
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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