Azidotrimethylsilane → HCID 178508632, compound

HRID 2237629Notes

Reaction equation

HRID 2237629 reaction equation
C[Al](C)C.C[Si]([N:9]=[N+:10]=[N-:11])(C)C.[NH2:12][C:13]1[C:18]2[C:19](=[O:39])[N:20]([C:24]3[CH:29]=[CH:28][C:27]([C@H:30]4[CH2:35][CH2:34][C@H:33]([CH2:36][C:37]#[N:38])[CH2:32][CH2:31]4)=[CH:26][CH:25]=3)[CH2:21][CH2:22][O:23][C:17]=2[N:16]=[CH:15][N:14]=1>C1(C)C=CC=CC=1>[NH2:12][C:13]1[C:18]2[C:19](=[O:39])[N:20]([C:24]3[CH:25]=[CH:26][C:27]([CH:30]4[CH2:31][CH2:32][CH:33]([CH2:36][C:37]5[NH:38][N:11]=[N:10][N:9]=5)[CH2:34][CH2:35]4)=[CH:28][CH:29]=3)[CH2:21][CH2:22][O:23][C:17]=2[N:16]=[CH:15][N:14]=1

Participants

5

Reactant 3

HCID 78378AzidotrimethylsilaneHCID 16682925TrimethylaluminumHCID 178511071HCID 178511071, compound

Product 1

HCID 178508632HCID 178508632, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a cooled 0° C., stirred solution of trimethylaluminum (2M in toluene, 0.33 mL) in toluene (0.66 mL) were added trimethylsilylazide (0.86 mL) and {trans-4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]cyclohexyl}acetonitrile (25 mg). This mixture was heated at 80° C. for 40 hours, cooled, concentrated in vacuo and chromatographed (4 g silica gel column, 0-10% methanol:chloroform) to afford the title compound as a white solid, 2.8 mg. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.96-1.28 (m, 2 H) 1.25-1.45 (m, 2H) 1.62-1.80 (m, 5H) 2.31-2.50 (m, 1H) 2.62-2.76 (m, 2H) 3.85-3.95 (m, 2H) 4.45-4.57 (m, 2H) 7.13-7.29 (m, 4H) 7.55 (br. s., 2H) 8.10 (s, 1H) m/z=421.3 (M+1). IC50 76.2 nM (range 47.5-163 nM).

Workup

  1. temperaturecooled
  2. concentrationconcentrated in vacuo
  3. customchromatographed (4 g silica gel column, 0-10% methanol:chloroform)

Sources & evidence

ORD record
ord-3db19348d73b432ba01657e6ed8d2c02
Source dataset
uspto-grants-2010_05
Patent number
US07718645B2

Reaction notes

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