Diisopropylethylamine → HCID 86691398, compound

HRID 540179Notes

Reaction equation

HRID 540179 reaction equation
[O:1]=[S:2]1(=[O:29])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][N:5]([C:13]2[CH:22]=[C:21]([NH:23][CH2:24][CH2:25][CH2:26][NH2:27])[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([CH3:28])[CH:19]=3)[N:14]=2)[CH2:4][CH2:3]1.[O:30]1[CH2:33][C:32](=O)[CH2:31]1.C(N(C(C)C)C(C)C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[O:29]=[S:2]1(=[O:1])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][N:5]([C:13]2[CH:22]=[C:21]([NH:23][CH2:24][CH2:25][CH2:26][NH:27][CH:32]3[CH2:33][O:30][CH2:31]3)[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([CH3:28])[CH:19]=3)[N:14]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydride2×HCID 150242543-OxetanoneHCID 71255859HCID 71255859, compound

Product 1

HCID 86691398HCID 86691398, compoundYield 27.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred of N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]propane-1,3-diamine (84 mg, 0.2 mmol, prepared in analogy to Example 9-3), oxetan-3-one (15 mg, 0.21 mmol) and ethyldiisopropylamine (43 μL, 0.25 mmol) in dichloromethane (10 mL) was added molecular sieves (4 Å, 84 mg) followed by sodium triacetoxyborohydride (63.6 mg, 0.3 mmol). After being stirred at room temperature overnight, another batch of sodium triacetoxyborohydride (63.6 mg, 0.3 mmol) was added and the mixture was heated under reflux for 2 hours. The reaction mixture was cooled, washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative HPLC to afford 26 mg of N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-N′-(oxetan-3-yl)propane-1,3-diamine as a white solid. MS obsd. (ESI+) [(M+H)+] 467, 1H NMR (400 MHz, CD3OD) δ ppm 8.05 (d, J=7.6 Hz, 1 H), 7.87 (d, J=7.6 Hz, 1 H), 7.34 (s, 1 H), 7.68 (t, J=14.8 Hz, 1 H), 7.58-7.51 (m, 2 H), 7.45 (d, 1 H), 5.99 (s, 1 H), 5.24 (s, 2 H), 4.85 (t, J=3.3 Hz, 2 H), 4.85 (t, J=13.6 Hz, 2 H), 4.55 (m, 4 H), 4.06-4.00 (m, 1 H), 3.67 (s, 2 H), 3.50 (t, J=13.2 Hz, 2 H), 2.74 (t, J=13.6 Hz, 2 H), 2.45 (s, 3 H), 1.98-1.91 (m, 2 H).

Workup

  1. additionwas added molecular sieves (4 Å, 84 mg)
  2. temperaturethe mixture was heated
  3. temperatureunder reflux for 2 hours
  4. temperatureThe reaction mixture was cooled
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-0394c1d7f8624c83adb224bed6a2f3db
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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