Triethylamine → HCID 54674009, compound

HRID 2363562Notes

Reaction equation

HRID 2363562 reaction equation
Cl.[CH3:2][CH:3]([CH3:15])[CH2:4][C@H:5]([N:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)[C:6]([OH:8])=O.C(N(CC)CC)C.O.ON1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C.[CH2:45]([N:52]1[CH2:56][C@H:55]2[C@H:57]([NH2:60])[CH2:58][CH2:59][C@H:54]2[CH2:53]1)[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1>ClCCl>[CH2:45]([N:52]1[CH2:56][C@H:55]2[C@H:57]([NH:60][C:6](=[O:8])[C@@H:5]([N:9]3[CH2:14][CH2:13][O:12][CH2:11][CH2:10]3)[CH2:4][CH:3]([CH3:2])[CH3:15])[CH2:58][CH2:59][C@H:54]2[CH2:53]1)[C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 25918977(3aS,4R,6aR)-2-benzyloctahydrocyclopenta[c]pyrrol-4-amineHCID 66589983HCID 66589983, compound

Product 1

HCID 54674009HCID 54674009, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-4-Methyl-2-morpholinopentanoic acid hydrochloride (363 mg, 1.526 mmol) and triethylamine (0.387 mL, 2.77 mmol) were combined in dichloromethane (10 mL). 1-Hydroxybenzotriazole hydrate (234 mg, 1.526 mmol) and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.270 mL, 1.526 mmol) were added, and the reaction was stirred for 15 minutes. Then (3aS,4R,6aR)-2-benzyloctahydrocyclopenta[c]pyrrol-4-amine (300 mg, 1.387 mmol) from Example 16 Step E was added, and the reaction mixture was stirred at ambient temperature for 24 hours. The reaction was quenched with aqueous sodium bicarbonate and extracted with dichloromethane. The solvent was removed in vacuo and the crude material was purified by silica gel chromatography using 1-10% methanol (2 N ammonia)/dichloromethane to give the title compound: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.27 (d, J=7.3, 1H), 7.44 (d, J=7.4, 2H), 7.37 (t, J=7.5, 2H), 7.27 (dd, J=9.8, 17.3, 1H), 4.51-4.39 (m, 1H), 3.74 (t, J=4.5, 4H), 3.62 (d, J=13.1, 1H), 3.45 (d, J=13.1, 1H), 3.29-3.21 (m, 1H), 2.87 (dd, J=2.4, 9.0, 1H), 2.79 (dt, J=4.5, 9.3, 2H), 2.75-2.68 (m, 2H), 2.55 (d, J=14.8, 2H), 2.49-2.43 (m, 1H), 2.35 (dd, J=2.6, 8.9, 1H), 2.32-2.26 (m, 1H), 2.11 (dq, J=6.1, 12.1, 1H), 1.86 (dd, J=6.6, 12.2, 3H), 1.67-1.55 (m, 2H), 1.41 (dt, J=6.2, 20.1, 1H), 0.94 (dd, J=6.2, 11.1, 6H); MS (ESI+) m/z 400 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature for 24 hours
  2. customThe reaction was quenched with aqueous sodium bicarbonate
  3. extractionextracted with dichloromethane
  4. customThe solvent was removed in vacuo
  5. customthe crude material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-79515d7d715d4b3995415369811b8078
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

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