Piconol → HCID 136436899, compound

HRID 990232Notes

Reaction equation

HRID 990232 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[OH:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1.C(O[C:22]1[C:27]([C:28]2[NH:29][C:30](=[O:47])[C:31]3[C:32](=[C:34]([CH2:44][CH2:45][CH3:46])[N:35]([CH2:37][C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=4)[N:36]=3)[N:33]=2)=[CH:26][C:25]([S:48]([N:51]2[CH2:56][CH2:55][N:54]([CH2:57][CH3:58])[CH2:53][CH2:52]2)(=[O:50])=[O:49])=[CH:24][N:23]=1)C>>[CH2:57]([N:54]1[CH2:55][CH2:56][N:51]([S:48]([C:25]2[CH:26]=[C:27]([C:28]3[NH:29][C:30](=[O:47])[C:31]4[C:32](=[C:34]([CH2:44][CH2:45][CH3:46])[N:35]([CH2:37][C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=5)[N:36]=4)[N:33]=3)[C:22]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)=[N:23][CH:24]=2)(=[O:50])=[O:49])[CH2:52][CH2:53]1)[CH3:58]

Participants

4

Reactant 3

HCID 11474PiconolHCID 3251421Potassium bis(trimethylsilyl)amideHCID 135485687HCID 135485687, compound

Product 1

HCID 136436899HCID 136436899, compoundYield 21%

Conditions

Temperature
100 °C

Procedure

A stirred mixture of potassium bis(trimethylsilyl)amide (260 mg, 1.32 mmol) and 2-hydroxymethylpyridine (5 ml) was heated at 100° C. for 1hour, then the title compound of Example 26 (150 mg, 0.26 mmol) added and the reaction mixture stirred at 100° C. for 14 hours. The resulting cool mixture was partitioned between dichloromethane (10 ml) and brine (10 ml), the phases separated and the aqueous phase extracted with dichloromethane (2×10 ml). The combined organic solutions were dried (MgSO4) and evaporated under reduced pressure, then the residual yellow oil purified by column chromatography on silica gel, using dichloromethane:ethyl acetate:methanol (47.5:47.5:5) as eluant, to afford the title compound (35 mg, 21%) as a white solid. δ (CDCl3): 0.94 (3H, t), 1.03 (3H, t), 1.73 (2H, m), 2.40 (2H, q), 2.55 (4H, m), 2.98 (2H, t), 3.14 (4H, m), 5.69 (2H, s), 5.92 (2H, s), 7.07 (1H, d), 7.21 (1H, m), 7.33 (2H, m), 7.62 (1H, m), 7.76 (1H, m), 8.58 (2H, m), 8.81 (1H, s), 8.85 (1H, d), 12.80 (1H, s). LRMS: m/z 630 (M+1)+.

Workup

  1. temperatureThe resulting cool mixture
  2. customwas partitioned between dichloromethane (10 ml) and brine (10 ml)
  3. customthe phases separated
  4. extractionthe aqueous phase extracted with dichloromethane (2×10 ml)
  5. dry with materialThe combined organic solutions were dried (MgSO4)
  6. customevaporated under reduced pressure
  7. customthe residual yellow oil purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-70b5ac4c83ea45f9a2426e86501d2302
Source dataset
uspto-grants-2002_10
Patent number
US06458951B2

Reaction notes

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