Hydrochloric Acid → {3,5-Dichloro-4-[7-fluoro-4-(6-methylpyrimidin-4-ylamino)pyrazolo[4,3-c]pyridin-2-yl]phenyl}methanol hydrochloride salt

HRID 626807Notes

Reaction equation

HRID 626807 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Cl:28])[C:9]=1[N:10]1[CH:27]=[C:13]2[C:14]([NH:19][C:20]3[CH:25]=[C:24]([CH3:26])[N:23]=[CH:22][N:21]=3)=[N:15][CH:16]=[C:17]([F:18])[C:12]2=[N:11]1)[CH:5]=[O:6].[BH4-].[Na+].Cl>C(O)C.C1COCC1>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([CH2:5][OH:6])[CH:7]=[C:8]([Cl:28])[C:9]=1[N:10]1[CH:27]=[C:13]2[C:14]([NH:19][C:20]3[CH:25]=[C:24]([CH3:26])[N:23]=[CH:22][N:21]=3)=[N:15][CH:16]=[C:17]([F:18])[C:12]2=[N:11]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 866970833,5-Dichloro-4-[7-fluoro-4-(6-methylpyrimidin-4-ylamino)pyrazolo[4,3-c]pyridin-2-yl]benzaldehyde

Product 1

HCID 69670988{3,5-Dichloro-4-[7-fluoro-4-(6-methylpyrimidin-4-ylamino)pyrazolo[4,3-c]pyridin-2-yl]phenyl}methanol hydrochloride saltYield 90.7%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3,5-dichloro-4-[7-fluoro-4-(6-methylpyrimidin-4-ylamino)pyrazolo[4,3-c]pyridin-2-yl]benzaldehyde (125 mg, 0.3 mmol) in ethanol (IMS grade, 5 mL) and THF (2 mL) was added sodium borohydride (14 mg, 0.36 mmol) and the reaction mixture was stirred at room temperature for 2 hours. The resultant mixture was partitioned between ethyl acetate and water and the layers were separated. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-1% methanol in ethyl acetate) to yield a solid, to which was added HCl (1.25 N in propan-2-ol, 10 mL) and the mixture was stirred at room temperature for 1 hour. The solid obtained was collected by filtration and dried to afford the title compound as an off-white solid (62 mg, 45% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.35 (br s, 1H), 8.97 (s, 1H), 8.36 (br s, 1H), 8.10 (d, J=3.5 Hz, 1H), 7.75 (s, 2H), 4.68 (s, 2H), 2.57 (s, 3H). LCMS (Method B): RT=2.89 min, m/z: 419 [M+H+].

Workup

  1. customThe resultant mixture was partitioned between ethyl acetate and water
  2. customthe layers were separated
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel flash chromatography (0-1% methanol in ethyl acetate)
  8. customto yield a solid
  9. stirringthe mixture was stirred at room temperature for 1 hour
  10. customThe solid obtained
  11. filtrationwas collected by filtration
  12. customdried

Sources & evidence

ORD record
ord-8910352a08764f3e8f5168487e8c430a
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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