HCID 480334, compound → HCID 480426, compound

HRID 429976Notes

Reaction equation

HRID 429976 reaction equation
[CH2:1]([C@H:8]([NH:33][C:34](=[O:44])[O:35][C@@H:36]1[C@H:43]2[C@H:39]([O:40][CH2:41][CH2:42]2)[O:38][CH2:37]1)[C@H:9]([OH:32])[CH2:10][N:11]([CH2:23][C:24]([CH3:31])([CH3:30])[CH2:25][CH2:26][CH2:27][C:28]#[N:29])[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]>[NH2:29][CH2:28][CH2:27][CH2:26][CH2:25][C:24]([CH3:31])([CH3:30])[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:32])[C@@H:8]([NH:33][C:34](=[O:44])[O:35][C@@H:36]1[C@H:43]2[C@H:39]([O:40][CH2:41][CH2:42]2)[O:38][CH2:37]1)[CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 1

HCID 480334HCID 480334, compound

Product 1

HCID 480426HCID 480426, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 935NickelCatalyst

Procedure

A mixture of 0.18 g (0.29 mmol) of (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl N-[(1S,2R)-1-benzyl-3-((5-cyano-2,2-dimethylpentyl)[3-(methylamino)phenyl]sulfonylamino)-2-hydroxypropyl]carbamate (obtained via a protocol directely analogous to Example (Compound 245)) and approximately 50 mg of Raney nickel (washed with water and then MeOH) in 40 mL of 2M NH3/MeOH was subjected to hydrogenation at 40 psi. After 1.5 hours the vessel was purged with nitrogen, catalyst removed by filtration through celite and the filtrate concentrated to dryness in vacuo. The residue was subjected to flash chromatography (SiO2, 9:1 CH2Cl2, 2M NH3 in MeOH) to afford 0.13 g (72%) of the desired amine as a white foam. H1-NMR (CDCl3): 7.31-7.12 (m, 6H), 7.01 (d, 1H), 6.92 (s, 1H), 6.75 (dd, 1H), 5.60 (d, 1H), 5.29 (d, 1H), 4.99 (q, 1H), 4.15 (br s, 1H), 4.00 (t, 1H), 3.89 (m, 1H), 3.80 (m, 2H), 3.67 (m, 2H), 3.21 (dd, 1H), 3.17-2.98 (m, 3H), 2.94-2.80 (m, 2H), 2.84 (s, 3H), 2.71 (m, 3H), 1.58 (m, 1H), 1.47-1.21 (m, 7H), 0.90 (s, 3H), 0.88 (s, 3H). MS(ESI): 633 (M+H).

Workup

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

Sources & evidence

ORD record
ord-84d93902ab4045b0b3cb5dd71b6746e0
Source dataset
uspto-grants-2001_11
Patent number
US06319946B1

Reaction notes

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