Diisobutylaluminumhydride → HCID 71115071, compound

HRID 468828Notes

Reaction equation

HRID 468828 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[CH:11]1([C:14]([NH:16][C:17]2[N:18]=[CH:19][C:20]3[C:25]([CH:26]=2)=[CH:24][CH:23]=[C:22]([C:27]2[C:28]([CH3:38])=[C:29]([F:37])[C:30]([C:33](OC)=[O:34])=[N:31][CH:32]=2)[CH:21]=3)=[O:15])[CH2:13][CH2:12]1>C(Cl)Cl>[F:37][C:29]1[C:28]([CH3:38])=[C:27]([C:22]2[CH:21]=[C:20]3[C:25]([CH:26]=[C:17]([NH:16][C:14]([CH:11]4[CH2:13][CH2:12]4)=[O:15])[N:18]=[CH:19]3)=[CH:24][CH:23]=2)[CH:32]=[N:31][C:30]=1[CH2:33][OH:34]

Participants

4

Reactant 2

HCID 21225700DiisobutylaluminumhydrideHCID 67975035HCID 67975035, compound

Product 1

HCID 71115071HCID 71115071, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-15 °C

Procedure

Diisobutylaluminum hydride (1.0M solution in tetrahydrofuran, 0.73 mL) was added dropwise to a solution of methyl 5-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-3-fluoro-4-methylpicolinate (60 mg, 1.8 mmol) in methylene chloride (1.5 mL) cooled at −15° C. After 1 hour at this temperature, the reaction was quenched by dropwise addition of saturated aqueous ammonium chloride solution (3 mL). The reaction mixture was diluted with ethyl acetate (50 mL) and washed with 1.0M citric acid solution in water (20 mL). The organic layer was separated, and the aqueous layer was neutralized via addition of solid sodium bicarbonate solution and then extracted with ethyl acetate (50 mL). The combined organic portions were dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min) to afford the title compound as an off-white solid (15 mg, 23%). 1H NMR (400 MHz, DMSO) δ 10.94 (s, 1H), 9.21 (s, 1H), 8.52 (s, 1H), 8.35 (s, 1H), 8.11 (s, 1H), 7.98 (d, J=8.6 Hz, 1H), 7.75 (d, J=8.6 Hz, 1H), 5.31 (s, 1H), 4.65 (s, 2H), 2.26 (s, 3H), 2.12-2.04 (m, 1H), 0.91-0.80 (m, 4H). LCMS (Method G): RT=7.53 min, M+H+=352.1.

Workup

  1. customthe reaction was quenched by dropwise addition of saturated aqueous ammonium chloride solution (3 mL)
  2. additionThe reaction mixture was diluted with ethyl acetate (50 mL)
  3. washwashed with 1.0M citric acid solution in water (20 mL)
  4. customThe organic layer was separated
  5. additionthe aqueous layer was neutralized via addition of solid sodium bicarbonate solution
  6. extractionextracted with ethyl acetate (50 mL)
  7. dry with materialThe combined organic portions were dried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customto afford a residue that
  11. customwas purified by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min)

Sources & evidence

ORD record
ord-7f0ae7f7fb554c83bd707376e2366f2d
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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