Hydrochloric Acid → HCID 11285018, compound

HRID 2099817Notes

Reaction equation

HRID 2099817 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:40]=[CH:41][CH:42]=1)[CH2:5][N:6]1[CH:10]=[C:9]([CH3:11])[N:8]=[C:7]1[CH:12]([NH:32][C:33](=[O:39])OC(C)(C)C)[CH2:13][C:14]1[CH:22]=[C:21]([CH3:23])[C:20]2[C:16](=[CH:17][N:18](COCC[Si](C)(C)C)[N:19]=2)[CH:15]=1.Cl.C(C1NC=CN=1)(C1NC=CN=1)=O.[NH:56]1[CH2:61][CH2:60][CH:59]([N:62]2[CH2:71][C:70]3[C:65](=[CH:66][CH:67]=[CH:68][CH:69]=3)[NH:64][C:63]2=[O:72])[CH2:58][CH2:57]1>C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:40]=[CH:41][CH:42]=1)[CH2:5][N:6]1[CH:10]=[C:9]([CH3:11])[N:8]=[C:7]1[CH:12]([NH:32][C:33]([N:56]1[CH2:57][CH2:58][CH:59]([N:62]2[CH2:71][C:70]3[C:65](=[CH:66][CH:67]=[CH:68][CH:69]=3)[NH:64][C:63]2=[O:72])[CH2:60][CH2:61]1)=[O:39])[CH2:13][C:14]1[CH:15]=[C:16]2[C:20](=[C:21]([CH3:23])[CH:22]=1)[NH:19][N:18]=[CH:17]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 110425973-(Piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-oneHCID 57794652HCID 57794652, compound

Product 1

HCID 11285018HCID 11285018, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

tert-Butyl 1-(1-(3-fluorobenzyl)-4-methyl-1H-imidazol-2-yl)-2-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)ethylcarbamate (20.0 mg, 0.034 mmol) was dissolved in a minimum amount of ethyl acetate, and treated with hydrochloric acid (4 N in dioxane, 1.0 mL). The mixture was stirred under nitrogen for 3 days. After removal of the solvents, the crude mixture was treated with diethyl ether to give a precipitate which was filtered. The resulting solid was dissolved in dimethylformamide (1.0 mL), cooled to 0° C., and treated with carbonyl diimidazole (6.0 mg, 0.037 mmol, 1.1 equiv) and N′N-diisopropylethylamine (24.3 μL, 3 equiv). The reaction was stirred for 5 min at 0° C., warmed to room temperature, stirred for 10 min, and treated with 3-(piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one (8.5 mg, 0.037 mmol, 1.1 equiv). The mixture was stirred at room temperature overnight. The solvent was evaporated and the residue purified by column chromatography to afford 16.1 mg (74%, 2 steps). 1H-NMR (CD3OD, 500 MHz) δ 1.50-1.68 (m, 4H), 2.27 (s, 3H), 2.46 (s, 3H), 2.77 (m, 2H), 3.20 (m, 2H), 4.01-4.16 (m, 2H), 4.20 (s, 2H), 4.32-4.43 (m, 1H), 5.13-5.22 (m, 2H), 6.60-6.67 (m, 2H), 6.70 (s, 1H), 6.76-6.86 (m, 2H), 6.87-6.94 (m, 1H), 6.96 (dd, J=8.3, 6.7, 1H), 7.07-7.14 (m, 2H), 7.16 (dd, J=7.9, 7.6, 1H), 7.25 (s, 1H), 7.92 (s, 1H). Mass spec.: 621.4 (MH)+.

Workup

  1. customAfter removal of the solvents
  2. additionthe crude mixture was treated with diethyl ether
  3. customto give a precipitate which
  4. filtrationwas filtered
  5. dissolutionThe resulting solid was dissolved in dimethylformamide (1.0 mL)
  6. stirringThe reaction was stirred for 5 min at 0° C.
  7. temperaturewarmed to room temperature
  8. stirringstirred for 10 min
  9. stirringThe mixture was stirred at room temperature overnight
  10. customThe solvent was evaporated
  11. customthe residue purified by column chromatography
  12. customto afford 16.1 mg (74%, 2 steps)

Sources & evidence

ORD record
ord-674ca6d11b034f6ab9972dbc52744887
Source dataset
uspto-grants-2009_08
Patent number
US07569578B2

Reaction notes

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