Acetic Acid → 2-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-N-{[3-(ethylamino)oxetan-3-yl]methyl}-6-methylquinolin-4-amine

HRID 540176Notes

Reaction equation

HRID 540176 reaction equation
[NH2:1][C:2]1([CH2:6][NH:7][C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([CH3:18])[CH:16]=3)[N:11]=[C:10]([N:19]3[CH2:25][C:24]4[CH:26]=[CH:27][CH:28]=[CH:29][C:23]=4[S:22](=[O:31])(=[O:30])[CH2:21][CH2:20]3)[CH:9]=2)[CH2:5][O:4][CH2:3]1.[CH:32](=O)[CH3:33].C(O)(=O)C.C([BH3-])#N.[Na+]>CO.O1CCCC1.C(OCC)(=O)C>[O:30]=[S:22]1(=[O:31])[C:23]2[CH:29]=[CH:28][CH:27]=[CH:26][C:24]=2[CH2:25][N:19]([C:10]2[CH:9]=[C:8]([NH:7][CH2:6][C:2]3([NH:1][CH2:32][CH3:33])[CH2:5][O:4][CH2:3]3)[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([CH3:18])[CH:16]=3)[N:11]=2)[CH2:20][CH2:21]1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 177AcetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 71255246Syncytial Virus Inhibitor-1

Product 1

HCID 712623832-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-N-{[3-(ethylamino)oxetan-3-yl]methyl}-6-methylquinolin-4-amineYield 20%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of N-[(3-aminooxetan-3-yl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine (200 mg, 0.46 mmol, prepared in analogy to Example 2-2), acetaldehyde (25.6 μL, 0.46 mmol) and acetic acid (270 μL) in methanol (8 mL) was added dropwize a solution of sodium cyanoborohydride (34 mg, 0.54 mmol) in tetrahydrofuran (0.5 mL). After being stirred for 12 hours at room temperature, the reaction mixture was diluted with ethyl acetate, washed with water and a saturated aqueous solution of sodium bicarbonate, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by preparative HPLC to afford 42 mg of the desired product as a white solid (yield was 20%). MS obsd. (ESI+) [(M+H)+] 467, 1H NMR (400 MHz, DMSO-d6) δ ppm 7.95 (d, J=1.9 Hz, 1 H), 7.89-7.87 (t, J=2.2 Hz, 1 H), 7.64-7.58 (m, J=6.0 Hz, 2 H), 7.49-7.45 (m, J=4.0 Hz, 1 H), 7.35 (d, J=2.1 Hz, 1 H), 7.27-7.24 (m, J=2.5 Hz, 1 H), 6.17 (s, 1 H), 5.11 (s, 2 H), 4.52 (d, 2 H), 4.37 (d, 4 H), 3.62-3.45 (t, J=2.4 Hz, 2 H), 3.58 (d, 2 H), 2.53 (m, 2 H), 2.37 (s, 3 H), 1.07-1.03 (t, J=3.6 Hz, 3 H).

Workup

  1. washwashed with water
  2. dry with materiala saturated aqueous solution of sodium bicarbonate, dried over sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-e9d173e33ba84ad8a2b56d34cad86e46
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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