Pyridine → HCID 11655774, compound

HRID 1994163Notes

Reaction equation

HRID 1994163 reaction equation
[Si]([O:8][CH2:9]/[C:10](=[CH:24]\[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([O:31][C:32]2[CH:37]=[CH:36][N:35]=[C:34]([C:38]3[NH:39][CH2:40][CH2:41][N:42]=3)[CH:33]=2)[CH:26]=1)/[C:11]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([CH3:23])([CH3:22])[CH3:21])[CH:15]=1)=[O:12])(C(C)(C)C)(C)C.N1C=CC=CC=1>C1COCC1.N1C=CC=CC=1.CCOC(C)=O>[C:20]([C:16]1[CH:15]=[C:14]([NH:13][C:11](=[O:12])/[C:10](/[CH2:9][OH:8])=[CH:24]/[C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([O:31][C:32]3[CH:37]=[CH:36][N:35]=[C:34]([C:38]4[NH:39][CH2:40][CH2:41][N:42]=4)[CH:33]=3)[CH:26]=2)[CH:19]=[CH:18][CH:17]=1)([CH3:23])([CH3:21])[CH3:22]

Participants

5

Reactant 2

HCID 1049PyridineHCID 58674616HCID 58674616, compound

Product 1

HCID 11655774HCID 11655774, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 16069498Pyridine tetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(E)-2-((tert-butyldimethylsilyloxy)methyl)-N-(3-tert-butylphenyl)-3-(3-(2-(4,5-dihydro-1H-imidazol-2-yl)pyridin-4-yloxy)phenyl)acrylamide (107 mg, 0.18 mmol) was dissolved in a 1:1 mixture of THF/pyridine (3 mL). The reaction mixture was cooled to 0° C. and 20 drops of HF/pyridine were added. The reaction was sealed and allowed to warm to rt over 5 h. The mixture was diluted with EtOAc and washed with sat. NaHCO3, dried over Na2SO4, filtered, and concentrated. Purification by column chromatography (SiO2, 0-10% MeOH with 1% NH4OH in DCM) provided B-140 (32 mg). LCMS, FA: Rt=1.21 min, [MH+ 471.0]. 1H NMR (300 MHz, d4-MeOH): δ 8.48 (d, 1H), 7.68 (t, 1H), 7.56-7.51 (m, 3H), 7.48-7.44 (m, 1H), 7.41 (d, 1H), 7.31 (t, 1H), 7.25 (t, 1H), 7.19-7.15 (m, 2H), 7.08-7.05 (dd, 1H), 4.52 (s, 2H), 3.75 (s, 4H), and 1.32 (s, 9H).

Workup

  1. customThe reaction was sealed
  2. temperatureto warm to rt over 5 h
  3. washwashed with sat. NaHCO3
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by column chromatography (SiO2, 0-10% MeOH with 1% NH4OH in DCM)
  8. customprovided B-140 (32 mg)

Sources & evidence

ORD record
ord-759667b40bea4221b33f439c07b65c2d
Source dataset
uspto-grants-2010_01
Patent number
US07652041B2

Reaction notes

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