Trifluoroacetic acid → N-[(3-Aminooxetan-3-yl)methyl]-2-(1,1-dioxido-8-phenoxy-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine

HRID 540153Notes

Reaction equation

HRID 540153 reaction equation
C([N:8](CC1C=CC=CC=1)[C:9]1([CH2:13][NH:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([CH3:25])[CH:23]=3)[N:18]=[C:17]([N:26]3[CH2:32][C:31]4[CH:33]=[CH:34][C:35]([O:37][C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=5)=[CH:36][C:30]=4[S:29](=[O:45])(=[O:44])[CH2:28][CH2:27]3)[CH:16]=2)[CH2:12][O:11][CH2:10]1)C1C=CC=CC=1.FC(F)(F)C(O)=O>CO.[OH-].[OH-].[Pd+2]>[NH2:8][C:9]1([CH2:13][NH:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([CH3:25])[CH:23]=3)[N:18]=[C:17]([N:26]3[CH2:32][C:31]4[CH:33]=[CH:34][C:35]([O:37][C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=5)=[CH:36][C:30]=4[S:29](=[O:44])(=[O:45])[CH2:28][CH2:27]3)[CH:16]=2)[CH2:12][O:11][CH2:10]1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71255779N-{[3-(Dibenzylamino)oxetan-3-yl]methyl}-2-(1,1-dioxido-8-phenoxy-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine

Product 1

HCID 71254453N-[(3-Aminooxetan-3-yl)methyl]-2-(1,1-dioxido-8-phenoxy-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amineYield 15.2%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

A mixture of N-{[3-(dibenzylamino)oxetan-3-yl]methyl}-2-(1,1-dioxido-8-phenoxy-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine (90 mg, 0.13 mmol), palladium hydroxide on carbon (40 mg) and trifluoroacetic acid (0.1 mL) in methanol (30.0 mL) was stirred at room temperature under hydrogen (2 bar) for 14 hours. Then the reaction mixture was filtered and concentrated in vacuo. The residue was purified by preparative HPLC to afford 10.5 mg of the desired product as a white solid (yield was 15.2%). MS obsd. (ESI+) [(M+H)+] 531, 1H NMR (400 MHz, CD3OD) δ ppm 7.86 (d, J=8.34 Hz, 1 H), 7.69 (s, 1 H), 7.52 (d, J=2.53 Hz, 1 H), 7.45 (d, J=8.59 Hz, 1 H), 7.42-7.35 (m, 2 H), 7.31 (dd, J=8.46, 1.64 Hz, 1 H), 7.25-7.13 (m, 2 H), 7.06-6.97 (m, 2 H), 6.21 (s, 1 H), 5.14 (brs, 2 H), 4.70-4.46 (m, 6 H), 3.68 (s, 2 H), 3.60 (brs, 2 H), 2.44 (s, 3 H).

Workup

  1. filtrationThen the reaction mixture was filtered
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-54d82602ad6745b0809ae47ba36a6370
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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