tert-Butanol → HCID 58746000, compound

HRID 2110488Notes

Reaction equation

HRID 2110488 reaction equation
[I:1][C:2]1[N:7]2[N:8]=[CH:9][CH:10]=[C:6]2[C:5](C(O)=O)=[CH:4][CH:3]=1.C([N:17]([CH:20](C)C)CC)(C)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:30])C=CC=CC=1.[C:40]([OH:44])([CH3:43])([CH3:42])[CH3:41]>C1(C)C=CC=CC=1>[C:40]([O:44][C:20](=[O:30])[NH:17][C:5]1[C:6]2[N:7]([N:8]=[CH:9][CH:10]=2)[C:2]([I:1])=[CH:3][CH:4]=1)([CH3:43])([CH3:42])[CH3:41]

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 81531DiisopropylethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 218748477-Iodopyrazolo[1,5-a]pyridine-4-carboxylic acid

Product 1

HCID 58746000HCID 58746000, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a clear solution of 7-iodo-pyrazolo[1,5-a]pyridine-4-carboxylic acid (23.4 g, 81.2 mmol) and diisopropylethylamine (65 mL) in tert-butanol (250 mL) and anhydrous toluene (200 mL) was added diphenyl phosphoryl azide (25 mL, 114 mmol) under argon. After the mixture was stirred at rt for 30 min, the temperature was raised slowly to 90° C. The mixture was stirred at 90° C. overnight and concentrated under reduced pressure to remove the solvents. The residue was partitioned between EtOAc (200 mL) and aqueous NaOH solution (2N, 75 mL). The aqueous solution was separated and extracted with EtOAc (100 mL). The combined organic solutions were washed with aqueous NaOH solution (1N, 75 mL), dried over Na2SO4, and concentrated under reduced pressure. Purification by silica gel flash chomatography eluting with EtOAc/heptane (gradient from 0:1 to 1:1 ratio) gave a brownish solid. Recrystallization in heptane with some EtOAc gave compound 777D (19.6 g, 67%) as a yellow solid. HPLC: 95% at 3.83 min (retention time) (YMC S5 ODS-A column 4.6×50 mm eluting with 10-90% aqueous methanol over 4 min containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm). MS (ES): m/z 360 [M+H]+.

Workup

  1. temperaturethe temperature was raised slowly to 90° C
  2. stirringThe mixture was stirred at 90° C. overnight
  3. concentrationconcentrated under reduced pressure
  4. customto remove the solvents
  5. customThe residue was partitioned between EtOAc (200 mL) and aqueous NaOH solution (2N, 75 mL)
  6. customThe aqueous solution was separated
  7. extractionextracted with EtOAc (100 mL)
  8. washThe combined organic solutions were washed with aqueous NaOH solution (1N, 75 mL)
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. customPurification by silica gel flash chomatography
  12. washeluting with EtOAc/heptane (gradient from 0:1 to 1:1 ratio)
  13. customgave a brownish solid
  14. customRecrystallization in heptane with some EtOAc

Sources & evidence

ORD record
ord-896734f94e5d4cd0890e2a0ec235f06d
Source dataset
uspto-grants-2009_04
Patent number
US07517904B2

Reaction notes

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