Triethylamine → HCID 42635163, compound

HRID 220210Notes

Reaction equation

HRID 220210 reaction equation
[O:1]1[CH:5]2[O:6][CH2:7][CH2:8][CH:4]2[CH:3]([O:9][C:10](=[O:44])[NH:11][CH:12]([CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH:13]([OH:36])[CH2:14][N:15]([CH2:32][CH:33]([CH3:35])[CH3:34])[S:16]([C:19]2[CH:31]=[CH:30][C:22]3[N:23]=[C:24](S(C)(=O)=O)[S:25][C:21]=3[CH:20]=2)(=[O:18])=[O:17])[CH2:2]1.[Cl-].[CH:46]1([N:51]2[CH2:56][CH2:55][CH:54]([NH3+:57])[CH2:53][CH2:52]2)[CH2:50][CH2:49][CH2:48][CH2:47]1.C(N(CC)CC)C.C([O-])([O-])=O.[Na+].[Na+]>O1CCCC1.O.CO>[NH3:11].[O:1]1[CH:5]2[O:6][CH2:7][CH2:8][CH:4]2[CH:3]([O:9][C:10](=[O:44])[NH:11][CH:12]([CH2:37][C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH:13]([OH:36])[CH2:14][N:15]([S:16]([C:19]2[CH:31]=[CH:30][C:22]3[N:23]=[C:24]([NH:57][CH:54]4[CH2:55][CH2:56][N:51]([CH:46]5[CH2:50][CH2:49][CH2:48][CH2:47]5)[CH2:52][CH2:53]4)[S:25][C:21]=3[CH:20]=2)(=[O:18])=[O:17])[CH2:32][CH:33]([CH3:34])[CH3:35])[CH2:2]1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 66720539HCID 66720539, compoundHCID 66720587HCID 66720587, compound

Product 2

HCID 222AmmoniaHCID 42635163HCID 42635163, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

{1-Benzyl-2-hydroxy-3-[isobutyl-(2-methanesulfonyl-benzothiazole-6-sulfonyl)-amino]-propyl}-carbamic acid hexahydro-furo[2,3-b]furan-3-yl ester (1)1,2 (10 g, 15 mmol, 1 equiv), 1-cyclopentyl-piperidin-4-yl-ammonium chloride (4) (6.02 g, 25 mmol, 1.67 equiv) and triethylamine (6.10 g, 60 mmol, 4 equiv) were dissolved in tetrahydrofurane (200 mL), followed by the addition of 10% Na2CO3 in water (50 mL). The solution was stirred at room temperature for 48 hours. The organic layer was separated and washed with saturated NaHCO3 solution. The organic layer was dried on MgSO4, filtered and evaporated under reduced pressure. The crude product was purified by column chromatography on elution with dichloromethane:ammonia in methanol (7N) (100 to 95:5) to yield the title compound (4.45 g, 15 mmol, 39%). LRMS (ES+): m/z 756 [M+H]+; HPLC (system 1) (290 nm) tR 4.16 min, 97.11%; 1H-NMR (CDCl3) 0.87 (d, 3H, J=6.48, CH3), 0.92 (d, 3H, J=6.50, CH3), 1.33-1.51 (m, 4H, CH2 (2×) (cyclopentyl)), 1.51-1.77 (m, 6H, CH2 (2×) (piperidine) and CH2, H4), 1.77-1.96 (m, 5H, CH2 (2×) (cyclopentyl) and CH (isobutyl)), 2.09-2.28 (m, 4H, CH2 (2×) (piperidine)), 2.43-2.59 (m, 1H, CH (cyclopentyl)), 2.72-2.85 (m, 1H, OH), 2.85-2.92 (m, 1H, CH, H3a), 2.92-3.12 (m, 5H, CH (piperidine) and CH2—N and CH2 (isobutyl)), 3.20 (dd, 2H, J=8.63 and J=15.16, CH2 of C6H5CH2), 3.58-3.79 (m, 3H, CH2, H5 and CH2, H2), 3.79-3.91 (m, 3H, CH2, H2 and CH—NH and CH—OH), 4.90-5.10 (m, 2H, CH, H3 and NH), 5.42-5.59 (m, 1H, NH), 5.62 (d, 1H, J=5.04, CH, H6a), 7.12-7.32 (m, 5H, C6H5), 7.52 (d, 1H, J=8.54, CH (benzthiazole)), 7.67 (dd, 1H, J=0.99 and J=8.47, CH (benzthiazole)), 7.95-8.02 (brs, 1H, CH (benzthiazole)). 1 Surleraux, D. L. N. G. et al. Broad spectrum 2-(substituted-amino)-benzothiazolesulfonamide HIV protease inhibitors/PCT Int. Apl. 2002, WO2002083657.2 Surleraux, D. L. N. G. et al. Design of HIV-1 Protease Inhibitors Active on Multidrug-Resistant Virus.; J. Med. Chem. 2005, 48, 1965-1973.

Workup

  1. customThe organic layer was separated
  2. washwashed with saturated NaHCO3 solution
  3. customThe organic layer was dried on MgSO4
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customThe crude product was purified by column chromatography on elution with dichloromethane

Sources & evidence

ORD record
ord-4ea6f57165e74d41b85f9585d6ceac2f
Source dataset
uspto-grants-2012_06
Patent number
US08202887B2

Reaction notes

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