Piconol → HCID 89463056, compound

HRID 1473280Notes

Reaction equation

HRID 1473280 reaction equation
[OH:1][CH:2]([C:7]1[N:12]([CH3:13])[C:11](=[O:14])[C:10]2[N:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22](OC)=[CH:21]C=3)[N:16]=[CH:17][C:9]=2[C:8]=1[C:27]1[C:28]([CH3:37])=[C:29]2[C:34](=[CH:35][CH:36]=1)[O:33][CH2:32][CH2:31][CH2:30]2)[C:3]([O:5][CH3:6])=[O:4].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:57]1C=CC=CC=1CO.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C(O)(C(F)(F)F)=O.C1COCC1.ClCCl>[OH:1][CH:2]([C:7]1[N:12]([CH3:13])[C:11](=[O:14])[C:10]2[N:15]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:57]=3)[N:16]=[CH:17][C:9]=2[C:8]=1[C:27]1[C:28]([CH3:37])=[C:29]2[C:34](=[CH:35][CH:36]=1)[O:33][CH2:32][CH2:31][CH2:30]2)[C:3]([O:5][CH3:6])=[O:4]

Participants

8

Reactant 4

HCID 11474PiconolHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 89462968HCID 89462968, compound

Product 1

HCID 89463056HCID 89463056, compoundYield 68%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 2-hydroxy-2-(1-(4-methoxybenzyl)-6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrazolo[3,4-c]pyridin-5-yl)acetate (100 mg, 0.2 mmol) in TFA (1 mL)/dichloromethane (1 mL) was stirred at 55° C. for 6 h and then concentrated. The residue was partitioned between EtOAc and saturated sodium bicarbonate/water. The organic phase was dried over sodium sulfate and concentrated. The residue was dissolved in THF (2.5 mL) and to this solution triphenylphosphine (103 mg, 0.4 mmol) and pyridine-2-ylmethanol (43 mg, 0.4 mmol) was added followed by DIAD (0.076 mL, 0.4 mmol) and the mixture was stirred at ambient temperature for 2.5 h. The mixture was concentrated and purified on silica using EtOAc/hexanes 0-50% to provide the title compound (47 mg, 68%). 1H NMR (400 MHz, CDCl3) δ ppm 8.6 s (1H), 6.8-7.8 (m, 5H), 6.7 (d, 1H), 6.2-6.4 (m, 2H), 5.3 (s, 1H), 4.3 (broad s, 2H), 3.9 (s, 3H), 3.7 (s, 3H), 2.7 (broad s, 2H), 2.0 (s, 3H), 1.7 (broad s, 2H); ES-LCMS: 475.2 (M+1).

Workup

  1. concentrationconcentrated
  2. customThe residue was partitioned between EtOAc and saturated sodium bicarbonate/water
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationconcentrated
  5. additionwas added
  6. concentrationThe mixture was concentrated
  7. custompurified on silica

Sources & evidence

ORD record
ord-20abe88e7d2a4820b4d0c634eb5bb57f
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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