Formaldehyde → HCID 77776214, compound

HRID 1934590Notes

Reaction equation

HRID 1934590 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1([CH2:58][N:59]2[CH:63]=[N:62][CH:61]=[N:60]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[CH:38]=[N:37][N:36]([CH:39]([CH3:56])[CH:40]([NH:42][CH:43]6[CH2:48][CH2:47][N:46]([CH2:49]C7C=CC=CC=7)[CH2:45][CH2:44]6)[CH3:41])[C:35]5=[O:57])=[CH:30][CH:29]=4)[CH2:24][CH2:23]3)=[CH:18][CH:17]=2)[CH2:11][O:10]1.C=O.S1C=CC=C1>C1COCC1.[Pd]>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1([CH2:58][N:59]2[CH:63]=[N:62][CH:61]=[N:60]2)[O:13][CH:12]([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([N:22]3[CH2:23][CH2:24][N:25]([C:28]4[CH:33]=[CH:32][C:31]([N:34]5[CH:38]=[N:37][N:36]([CH:39]([CH3:56])[CH:40]([NH:42][CH:43]6[CH2:44][CH2:45][N:46]([CH3:49])[CH2:47][CH2:48]6)[CH3:41])[C:35]5=[O:57])=[CH:30][CH:29]=4)[CH2:26][CH2:27]3)=[CH:18][CH:17]=2)[CH2:11][O:10]1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 8030ThiopheneHCID 22466429HCID 22466429, compound

Product 1

HCID 77776214HCID 77776214, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of [2S-[2α,4α(R*,S*)]]+[2S-[2α,4α(S*,R*)]]-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-2-[2-[[1-(phenylmethyl)-4-piperidinyl]amino]-1-methylpropyl]-3H-1,2,4-triazol-3-one (0.006 mol) in THF (250 ml) was hydrogenated for 3 days with Pd on activated carbon 10% (2 g) as a catalyst. Then paraformaldehyde (0.006 mol) and thiophene solution 4% (2 ml) were added. Hydrogenation was continued at 50° C. After uptake of H2, the mixture was cooled. The catalyst was filtered off and the filtrate was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5). The pure fractions were collected and the solvent was evaporated. The residue was crystallized from 2-propanol. The precipitate was filtered off and dried, yielding 3.2 g (68%) of [2S-[2α,4α(R*,S*)]]+[2S-[2α,4α(S*,R*)]]-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-2-[2-[(1-methyl-4-piperidinyl)amino]-1-methylpropyl]-3H-1,2,4-triazol-3-one (compound 64).

Workup

  1. customwas continued at 50° C
  2. temperatureAfter uptake of H2, the mixture was cooled
  3. filtrationThe catalyst was filtered off
  4. customthe filtrate was evaporated
  5. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5)
  6. customThe pure fractions were collected
  7. customthe solvent was evaporated
  8. customThe residue was crystallized from 2-propanol
  9. filtrationThe precipitate was filtered off
  10. customdried

Sources & evidence

ORD record
ord-a888c4de147046eda2f98828ba0dac4a
Source dataset
uspto-grants-2002_05
Patent number
US06384030B1

Reaction notes

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