Lithium Hydroxide → HCID 15486068, compound

HRID 2416714Notes

Reaction equation

HRID 2416714 reaction equation
[Li+].[OH-].[N:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:31]=[CH:30][C:17]2[CH2:18][CH:19]([CH2:25][C:26]([O:28]C)=[O:27])[C:20](=[O:24])[N:21]([CH3:23])[CH2:22][C:16]=2[CH:15]=1.C(O)(C(F)(F)F)=O>C1COCC1.O>[N:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:31]=[CH:30][C:17]2[CH2:18][CH:19]([CH2:25][C:26]([OH:28])=[O:27])[C:20](=[O:24])[N:21]([CH3:23])[CH2:22][C:16]=2[CH:15]=1

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 6422Trifluoroacetic acidHCID 22632146HCID 22632146, compound

Product 1

HCID 15486068HCID 15486068, compoundYield 126.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

1.0 N LiOH (0.80 mL, 0.80 mmole) was added to a solution of methyl (±)-8-[3-(2-pyridylamino)-1-propyloxy]-2-methyl-3-oxo-2,3,4,5-tetrahydro-1H-2-benzazepine-4-acetate (207.5 mg, 0.52 mmole) in THF (2.6 mL) and H2O (1.8 mL) at RT. The initially cloudy solution became homogeneous within 1 min. After 18 hr, the reaction was acidified with TFA (0.12 mL, 1.56 mmole) and concentrated. ODS chromatography (20% CH3CN/H2O containing 0.1% TFA), concentration, and lyophilization gave the title compound (252.4 mg, 83%) as a light yellow, hygroscopic solid: HPLC (PRP-1®, 20% CH3CN/H2O containing 0.1% TFA) K′=2.4; 1H NMR (400 MHz, CD3OD) δ 7.83-7.93 (m, 1 H), 7.76-7.83 (m, 1 H), 7.00-7.11 (m, 2 H), 6.83-6.91 (m, 1 H), 6.80 (dd, J=8.4, 2.6 Hz, 1 H), 6.76 (d, J=2.6 Hz, 1 H), 5.30 (d, J=16.5 Hz, 1 H), 4.05-4.18 (m, 2 H), 3.94 (d, J=16.5 Hz, 1 H), 3.77-3.90 (m, 1 H), 3.57 (t, J=6.8 Hz, 2 H), 3.03 (dd, J=17.0, 4.2 Hz, 1 H), 2.99 (s, 3 H), 2.83 (dd, J=17.0, 9.1 Hz, 1 H), 2.72 (dd, J=17.0, 13.5 Hz, 1 H), 2.44 (dd, J=17.0, 4.7 Hz, 1 H), 2.11-2.23 (m, 2 H); MS (ES) m/e 384 (M+H)+. Anal. Calcd for C21H25N3O4.1.5 CF3CO2H.1.5 H2O: C, 49.57; H, 5.11; N, 7.23. Found: C, 49.65; H, 4.95; N, 7.15.

Workup

  1. waitAfter 18 hr
  2. concentrationconcentrated
  3. concentrationODS chromatography (20% CH3CN/H2O containing 0.1% TFA), concentration, and lyophilization

Sources & evidence

ORD record
ord-ab41c7fb885740d597510047b424008d
Source dataset
uspto-grants-2004_11
Patent number
US06825188B2

Reaction notes

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