HCID 480312, compound → HCID 480397, compound

HRID 1167283Notes

Reaction equation

HRID 1167283 reaction equation
[CH2:1]([C@H:8]([NH:32][C:33](=[O:43])[O:34][C@@H:35]1[C@H:42]2[C@H:38]([O:39][CH2:40][CH2:41]2)[O:37][CH2:36]1)[C@H:9]([OH:31])[CH2:10][N:11]([CH2:23][C:24]([CH3:30])([CH3:29])[CH2:25][CH2:26][C:27]#[N:28])[S:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][CH3:22])[CH:16]=1)(=[O:14])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>[Ni].N.CO>[NH2:28][CH2:27][CH2:26][CH2:25][C:24]([CH3:30])([CH3:29])[CH2:23][N:11]([S:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][CH3:22])[CH:16]=1)(=[O:14])=[O:13])[CH2:10][C@@H:9]([OH:31])[C@@H:8]([NH:32][C:33](=[O:43])[O:34][C@@H:35]1[C@H:42]2[C@H:38]([O:39][CH2:40][CH2:41]2)[O:37][CH2:36]1)[CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 1

HCID 480312HCID 480312, compound

Product 1

HCID 480397HCID 480397, compoundYield 77.3%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 21705897Ammonia methanolSolvent

Procedure

A mixture of 0.29 g (0.46 mmol) of (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl N-[(1S, 2R)-1-benzyl-3-((4-cyano-2,2-dimethylbutyl)[3-(methylamino)phenyl]sulfonylamino)-2-hydroxypropyl]carbamate and approximately 50 mg of Raney nickel (washed with water and MeOH) in 60 mL of 2M NH3/MeOH was subjected to hydrogenation at 45 psi. After 1.5 hours the reaction vessel was purged with nitrogen, catalyst removed by filtration through celite and the filtrate concentrated in vacuo. The residue was subjected to flash chromatography (SiO2, 9:1 CH2Cl2/2M NH3 in MeOH) to afford 0.22 g (76%) of the desired amine as a white foam. NMR (CDCl3): 7.39-7.19 (m, 6H), 7.10 (d, 1H), 7.04-6.92 (m, 2H), 6.81 (dd, 1H), 5.63 (d, 1H), 5.05 (q, 1H), 4.16 (br s, 1H), 4.09-3.80 (m, 4H), 3.70 (m, 2H), 3.31 (m, 2H), 3.21-3.00 (m, 3H), 2.99-2.58 (m, 5H), 2.90 (s, 3H), 2.57-2.10 (br, 2H), 1.82-1.07 (m, 6H), 1.04 (s, H), 0.92 (s, 3H). MS(ESI): 619(M+H).

Workup

  1. customAfter 1.5 hours the reaction vessel was purged with nitrogen, catalyst
  2. customremoved by filtration through celite
  3. concentrationthe filtrate concentrated in vacuo

Sources & evidence

ORD record
ord-cf298f9bc621426a99f6376f02bfa9b0
Source dataset
uspto-grants-2003_09
Patent number
US06617350B2

Reaction notes

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