Sodium Hydroxide → 4-({[3-(Aminomethyl)oxetan-3-yl]methyl}amino)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinoline-6-carboxylic acid

HRID 540286Notes

Reaction equation

HRID 540286 reaction equation
[NH2:1][CH2:2][C:3]1([CH2:7][NH:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([C:19]([O:21]C)=[O:20])[CH:17]=3)[N:12]=[C:11]([N:23]3[CH2:29][C:28]4[CH:30]=[CH:31][CH:32]=[CH:33][C:27]=4[S:26](=[O:35])(=[O:34])[CH2:25][CH2:24]3)[CH:10]=2)[CH2:6][O:5][CH2:4]1.[OH-].[Na+]>O1CCCC1.O>[NH2:1][CH2:2][C:3]1([CH2:7][NH:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([C:19]([OH:21])=[O:20])[CH:17]=3)[N:12]=[C:11]([N:23]3[CH2:29][C:28]4[CH:30]=[CH:31][CH:32]=[CH:33][C:27]=4[S:26](=[O:35])(=[O:34])[CH2:25][CH2:24]3)[CH:10]=2)[CH2:4][O:5][CH2:6]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 71255152Methyl 4-({[3-(aminomethyl)oxetan-3-yl]methyl}amino)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinoline-6-carboxylate

Product 1

HCID 712554954-({[3-(Aminomethyl)oxetan-3-yl]methyl}amino)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinoline-6-carboxylic acidYield 20.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of methyl 4-({[3-(aminomethyl)oxetan-3-yl]methyl}amino)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinoline-6-carboxylate (100 mg, 0.2 mmol) in tetrahydrofuran and water (4 mL, V/V=3/1) was added sodium hydroxide (40 mg, 1.0 mmol). After being stirred at room temperature overnight, the resulting mixture was concentrated in vacuo to remove the organic solvent. The residual aqueous solution was acidified with an aqueous solution of citric acid (5 mL, 20%) and extracted with dichloromethane (15 mL×3). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo to afford a sticky solid, which was purified by flash column chromatography (eluting with 5% methanol in dichloromethane) to afford 20 mg of the desire product as a solid. MS obsd. (ESI+) [(M+H)+] 483, 1H NMR (400 MHz, DMSO-d6) δ ppm 8.78 (s, 1 H), 8.01 (d, 1 H), 7.90 (m, 2 H), 7.61 (t, 1 H), 7.47 (t, 1 H), 7.32 (d, 1 H), 6.29 (s, 1 H), 5.76 (s, 2 H), 4.40 (m, 6 H), 3.78 (s, 2 H), 3.62 (s, 2 H), 3.17 (m, 2 H).

Workup

  1. concentrationthe resulting mixture was concentrated in vacuo
  2. customto remove the organic solvent
  3. extractionextracted with dichloromethane (15 mL×3)
  4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto afford a sticky solid, which
  7. customwas purified by flash column chromatography (eluting with 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-b75552ee0caa486f92833e42ab1fbf79
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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