Hydrazine → (S)-1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-amine

HRID 870900Notes

Reaction equation

HRID 870900 reaction equation
[CH:1]1[CH:6]=[N:5][CH:4]=[C:3]2[CH2:7][O:8][C:9]3[CH:10]=[C:11]([O:15][CH2:16][C@@H:17]([N:22]4C(=O)C5C(=CC=CC=5)C4=O)[CH2:18][CH:19]([CH3:21])[CH3:20])[CH:12]=[CH:13][C:14]=3[C:2]=12.NN>C(O)C>[CH:1]1[CH:6]=[N:5][CH:4]=[C:3]2[CH2:7][O:8][C:9]3[CH:10]=[C:11]([O:15][CH2:16][C@@H:17]([NH2:22])[CH2:18][CH:19]([CH3:20])[CH3:21])[CH:12]=[CH:13][C:14]=3[C:2]=12

Participants

4

Reactant 2

HCID 9321HydrazineHCID 86695893(S)-2-(1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dione

Product 1

HCID 71728306(S)-1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-amineYield 39%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
45 °C

Procedure

To the solution of (S)-2-(1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dione (1.47 g, 3.43 mmol) in ethanol (8 mL) under a nitrogen atmosphere was added hydrazine (0.754 mL, 24.02 mmol) at rt and the reaction mixture was then stirred at 45° C. in an oil bath for 3 h. A white precipitate formed during the course of the reaction. The reaction mixture was quenched by addition of water (15 mL) and the product was extracted with ethyl acetate (3×25 mL). The combined organic extracts were dried with sodium sulfate and concentrated under reduced pressure. The residue was purified by preparative HPLC on a reverse phase C-18 column using 10 mM ammonium acetate buffer and acetonitrile gradient. The fractions were concentrated under reduced pressure and lyophilized to yield (S)-1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-amine (0.4 g, 0.970 mmol, 39% yield) as a yellow solid. 1H NMR (400 MHz, CD3OD) δ 8.48 (d, J=5.6 Hz, 1H), 8.37 (s, 1H), 7.86 (d, J=8.8 Hz, 1H), 7.70 (d, J=5.2 Hz, 1H), 6.83 (dd, J=8.4, 2.4, 1H), 6.70 (d, J=2.4 Hz, 1H), 5.20 (s, 2H), 4.28 (dd, J=11.2, 3.6, 1H), 4.10 (dd, J=10.4, 6.4, 1H), 3.66 (m, 1H), 1.82 (m, 1H), 1.69-1.63 (m, 2H), 1.04 (m, 6H); LCMS (ESI) m/e 299.2 [(M+H)+, calcd for C18H22N2O2 299.38]; LC/MS retention time (Method E): tR=1.78 min. HPLC retention time (method A): tR=7.97 min; CHIRAL HPLC retention time (method C): tR=12.87 min; optical rotation: [α]20D (MeOH)=+7.1°.

Workup

  1. customA white precipitate formed during the course of the reaction
  2. customThe reaction mixture was quenched by addition of water (15 mL)
  3. extractionthe product was extracted with ethyl acetate (3×25 mL)
  4. dry with materialThe combined organic extracts were dried with sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by preparative HPLC on a reverse phase C-18 column
  7. concentrationThe fractions were concentrated under reduced pressure

Sources & evidence

ORD record
ord-db1460cb52634103ac0b627c16f04c0f
Source dataset
uspto-grants-2015_03
Patent number
US08969564B2

Reaction notes

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