Tetrahydrofuran → HCID 71115166, compound

HRID 468915Notes

Reaction equation

HRID 468915 reaction equation
[CH:1]1([C:4]([NH:6][C:7]2[N:8]=[CH:9][C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[C:12]([C:17]2[CH:18]=[C:19]([CH:32]=[CH:33][C:34]=2[CH3:35])[C:20]([NH:22][C:23]2([C:27](OCC)=[O:28])[CH2:26][CH2:25][CH2:24]2)=[O:21])[CH:11]=3)=[O:5])[CH2:3][CH2:2]1.O1CCCC1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[CH:1]1([C:4]([NH:6][C:7]2[N:8]=[CH:9][C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[C:12]([C:17]2[CH:18]=[C:19]([CH:32]=[CH:33][C:34]=2[CH3:35])[C:20]([NH:22][C:23]2([CH2:27][OH:28])[CH2:26][CH2:25][CH2:24]2)=[O:21])[CH:11]=3)=[O:5])[CH2:2][CH2:3]1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 21226445Aluminium lithium hydride2×HCID 68095365HCID 68095365, compound

Product 1

HCID 71115166HCID 71115166, compoundYield 10.5%

Conditions

Temperature
0 °C

Procedure

To a solution of ethyl 1-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylbenzamido)cyclobutanecarboxylate (153.8 mg; 0.3261 mmol) in tetrahydrofuran (5.0 mL; 62 mmol) at 0° C. was dropwise added lithium aluminum hydride (1.0 M in THF) (0.50 mL; 0.50 mmol). The reaction mixture was stirred at 0° C. for 1.5 hours, followed by the addition of lithium aluminum hydride (1.0 M in THF) (0.20 mL; 0.2 mmol). After an additional 3 hours, the reaction was quenched by the sequential addition of 27 μL water, 27 μL 15% aqueous NaOH, and 80 μL water. The reaction mixture was diluted with dichloromethane, dried over MgSO4, filtered through celite, and evaporated in vacuo to yield 109.2 mg crude product. 36.8 mg of the crude product was purified via preparatory reverse-phase HPLC and lyophilized to yield 14.7 mg of the title compound. LCMS (ESI): RT=3.55, M+H=430.3, method=H; 1H NMR (400 MHz, DMSO) δ 10.90 (s, 1H), 9.19 (s, 1H), 8.51 (s, 1H), 8.24 (s, 1H), 8.04 (s, 1H), 7.94 (d, J=8.5 Hz, 1H), 7.86 (s, 1H), 7.81 (d, J=8.0 Hz, 1H), 7.73 (d, J=8.5 Hz, 1H), 7.42 (d, J=8.0 Hz, 1H), 4.78 (t, J=5.8 Hz, 1H), 3.64 (d, J=5.8 Hz, 2H), 2.32 (s, 3H), 2.24 (m, 2H), 2.17-2.01 (m, 3H), 1.91-1.63 (m, 2H), 0.85 (m, 4H).

Workup

  1. customat 0° C.
  2. waitAfter an additional 3 hours
  3. customthe reaction was quenched by the sequential addition of 27 μL water, 27 μL 15% aqueous NaOH, and 80 μL water
  4. additionThe reaction mixture was diluted with dichloromethane
  5. dry with materialdried over MgSO4
  6. filtrationfiltered through celite
  7. customevaporated in vacuo
  8. customto yield 109.2 mg crude product
  9. custom36.8 mg of the crude product was purified via preparatory reverse-phase HPLC

Sources & evidence

ORD record
ord-e9b16bbbf63d47a09c08b23fa605a50c
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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