Imidazole → HCID 10909025, compound

HRID 2306208Notes

Reaction equation

HRID 2306208 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[C:9]2[N:12]2[CH2:16][CH2:15][C@H:14]([NH:17][C:18](=[O:44])[CH2:19][C:20]3[N:21]=[CH:22][N:23]([C:25]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH:24]=3)[C:13]2=[O:45])=[CH:4][CH:3]=1.[Si:46](Cl)([C:59]([CH3:62])([CH3:61])[CH3:60])([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1.N1C=CN=C1>>[Si:46]([O:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[C:9]2[N:12]2[CH2:16][CH2:15][C@H:14]([NH:17][C:18](=[O:44])[CH2:19][C:20]3[N:21]=[CH:22][N:23]([C:25]([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)([C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=4)[C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH:24]=3)[C:13]2=[O:45])=[CH:4][CH:3]=1)([C:59]([CH3:62])([CH3:61])[CH3:60])([C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1

Participants

4

Reactant 3

HCID 795ImidazoleHCID 94078tert-ButyldiphenylchlorosilaneHCID 70170745HCID 70170745, compound

Product 1

HCID 10909025HCID 10909025, compound

Conditions

Temperature
50 °C

Procedure

A mixture of (S)-N-[1-(7-hydroxynaphthalen-1-yl)-2-oxopyrrolidin-3-yl]-2-[1-(triphenylmethyl)-1H-imidazol-4-yl]acetamide, as described above in Step C, (6.50 g, 11.0 mmol), tert-butyldiphenylsilyl chloride (4.55 g, 16.6 mol), and imidazole (1.87 g, 27.5 mol) in dry, degassed DMF (100 mL) was stirred, under argon, at 50° C. for 18 hours. The solvent was removed under reduced pressure and the residue was partitioned between saturated aqueous NaHCO3 (75 mL) and CH2Cl2 (125 mL). The aqueous layer was extracted further with CH2Cl2 (125 mL) and the combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography on silica, eluting with CH2Cl2—1% MeOH—0.1% NH4OH to yield the desired product as a pale solid.

Workup

  1. customin dry
  2. customdegassed DMF (100 mL)
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was partitioned between saturated aqueous NaHCO3 (75 mL) and CH2Cl2 (125 mL)
  5. extractionThe aqueous layer was extracted further with CH2Cl2 (125 mL)
  6. dry with materialthe combined organic extracts were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash column chromatography on silica
  10. washeluting with CH2Cl2—1% MeOH—0.1% NH4OH

Sources & evidence

ORD record
ord-3c83d2aa5ee040fd996a8ea1feea37cc
Source dataset
uspto-grants-2002_08
Patent number
US06441017B1

Reaction notes

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