Lithium aluminum hydride → HCID 67974361, compound

HRID 468760Notes

Reaction equation

HRID 468760 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:30])=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([NH:18][C:19]4[CH:20]=[C:21]([CH:26]=[C:27]([CH3:29])[N:28]=4)[C:22](OC)=[O:23])[N:14]=[CH:15]3)=[CH:10][CH:9]=2)[CH:7]=1.[AlH4-].[Li+]>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:30])=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([NH:18][C:19]4[CH:20]=[C:21]([CH2:22][OH:23])[CH:26]=[C:27]([CH3:29])[N:28]=4)[N:14]=[CH:15]3)=[CH:10][CH:9]=2)[CH:7]=1

Participants

4

Reactant 2

HCID 28112Lithium aluminum hydrideHCID 67975082HCID 67975082, compound

Product 1

HCID 67974361HCID 67974361, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of methyl 2-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-ylamino)-6-methylisonicotinate (prepared as described for Example 13, using methyl 2-bromo-6-methylisonicotinate) (55.0 mg, 0.137 mmol) in tetrahydrofuran (5.0 mL, 62 mmol) at 0° C. was slowly added 1.0 M of lithium tetrahydroaluminate in tetrahydrofuran (0.20 mL). The reaction was stirred at 0° C. for 30 minutes, and then quenched by the sequential addition of 8 μL water, then 8 μL 15% aq NaOH, then 23 μL water. The resulting mixture was diluted with dichloromethane and stirred at room temperature for 10 minutes, then dried with MgSO4 and filtered through celite. The solution was evaporated in vacuo and the crude product was purified via reverse phase HPLC and lyophilized to yield 20.8 mg (41%) of (2-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-ylamino)-6-methylpyridin-4-yl)methanol. LCMS (ESI): RT (min)=4.542, M+H=374.1, method=E; 1H NMR (400 MHz, DMSO-d6) δ 9.68 (s, 1H), 9.10 (s, 1H), 8.54 (s, 1H), 7.95 (s, 1H), 7.82 (d, J=8.6 Hz, 1H), 7.63 (dd, J=8.5, 1.6 Hz, 1H), 7.42-7.29 (m, 1H), 7.22-7.06 (m, 3H), 6.68 (s, 1H), 5.29 (t, J=5.4 Hz, 1H), 4.46 (d, J=4.7 Hz, 2H), 2.47 (s, 3H), 2.27 (s, 3H).

Workup

  1. customat 0° C.
  2. customquenched by the sequential addition of 8 μL water
  3. additionThe resulting mixture was diluted with dichloromethane
  4. stirringstirred at room temperature for 10 minutes
  5. dry with materialdried with MgSO4
  6. filtrationfiltered through celite
  7. customThe solution was evaporated in vacuo
  8. customthe crude product was purified via reverse phase HPLC

Sources & evidence

ORD record
ord-adf53c5520b64e6cb075005cf9e22c8f
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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