HCID 77775884, compound → HCID 77792329, compound

HRID 1934593Notes

Reaction equation

HRID 1934593 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1([CH2:54][N:55]2[CH:59]=[N:58][CH:57]=[N:56]2)[O:13][CH:12]([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([N:22]3[CH2:27][CH2:26][N:25]([C:28]4[CH:33]=[CH:32][C:31]([N:34]5[C:38](=[O:39])[N:37]([CH:40]([CH3:53])[CH:41]([NH:43][CH:44]([C:47]6[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=6)[C:45]#[N:46])[CH3:42])[N:36]=[CH:35]5)=[CH:30][CH:29]=4)[CH2:24][CH2:23]3)=[CH:18][CH:17]=2)[CH2:11][O:10]1.[H][H]>CO.N.[Ni]>[NH2:46][CH2:45][CH:44]([NH:43][CH:41]([CH3:42])[CH:40]([N:37]1[C:38](=[O:39])[N:34]([C:31]2[CH:32]=[CH:33][C:28]([N:25]3[CH2:24][CH2:23][N:22]([C:19]4[CH:18]=[CH:17][C:16]([O:15][CH2:14][CH:12]5[CH2:11][O:10][C:9]([C:3]6[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=6[F:1])([CH2:54][N:55]6[CH:59]=[N:58][CH:57]=[N:56]6)[O:13]5)=[CH:21][CH:20]=4)[CH2:27][CH2:26]3)=[CH:29][CH:30]=2)[CH:35]=[N:36]1)[CH3:53])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1

Participants

5

Reactant 2

HCID 77775884HCID 77775884, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 77792329HCID 77792329, compoundYield 15.4%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 21705897Ammonia methanolSolvent

Procedure

A mixture of compound 122 (0.003 mol) in CH3OH NH3 (200 ml) was hydrogenated overnight with Raney Nickel (1 g) as a catalyst. After uptake of hydrogen (2 equivalents), the catalyst was filtered off and the filtrate was evaporated. The residue was triturated in DIPE and 2-propanol, filtered off and dried. The residue was purified by HPLC (eluent: (ammonium acetate 0.5% in H2O/CH3CN 90/10)/CH3CN 90/10 to 0/100; column: HYPERPREP C18 BDS 8 μm). Two pure fractions were collected and their solvents were evaporated. The residue was triturated in DIPE, filtered off and dried, yielding 0.45 g [2S-[2α,4α[(S*,R*)(A)]]]-2-[2-[(2-amino-1-phenylethyl)amino]-1-methylpropyl]-4-[4-[4-[4-[[2-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]phenyl]-2,4-dihyro-3H-1,2,4-triazol-3-one (18.7%) (compound 174) and 0.37 g [2S-[2α,4α[(S*,R*)(B)]]]-2-[2[(2-amino-1-phenylethyl)amino]-1-methylpropyl]-4-[4-[4-[4-[[2-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]-phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (15.4%) (compound 178).

Workup

  1. customthe filtrate was evaporated
  2. customThe residue was triturated in DIPE and 2-propanol
  3. filtrationfiltered off
  4. customdried
  5. customThe residue was purified by HPLC (eluent: (ammonium acetate 0.5% in H2O/CH3CN 90/10)/CH3CN 90/10 to 0/100; column: HYPERPREP C18 BDS 8 μm)
  6. customTwo pure fractions were collected
  7. customtheir solvents were evaporated
  8. customThe residue was triturated in DIPE
  9. filtrationfiltered off
  10. customdried

Sources & evidence

ORD record
ord-6451b883d8a44a01a0bab6a00a479c23
Source dataset
uspto-grants-2002_05
Patent number
US06384030B1

Reaction notes

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