Heptane → (S)-2-((tert-Butyl dimethylsilyloxy)methyl)-N-(1-(3-(3-chloro-4-cyano phenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carboxamide

HRID 1409428Notes

Reaction equation

HRID 1409428 reaction equation
[NH2:1][C@@H:2]([CH3:18])[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[C:11]([Cl:17])[CH:10]=2)=[N:5]1.C[Al](C)C.CCCCCCC.[C:30]([Si:34]([CH3:55])([CH3:54])[O:35][CH2:36][C:37]1[N:38]([CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:53])([CH3:52])[CH3:51])[CH:39]=[C:40]([C:42](OC)=[O:43])[N:41]=1)([CH3:33])([CH3:32])[CH3:31]>C1(C)C=CC=CC=1.O>[Si:34]([O:35][CH2:36][C:37]1[N:38]([CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:51])([CH3:52])[CH3:53])[CH:39]=[C:40]([C:42]([NH:1][C@@H:2]([CH3:18])[CH2:3][N:4]2[CH:8]=[CH:7][C:6]([C:9]3[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[C:11]([Cl:17])[CH:10]=3)=[N:5]2)=[O:43])[N:41]=1)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:55])[CH3:54]

Participants

7

Reactant 4

HCID 8900HeptaneHCID 16682925TrimethylaluminumHCID 67170882(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrileHCID 86714656Methyl 2-((tert-butyldimethylsilyloxy)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carboxylate

Product 1

HCID 86714657(S)-2-((tert-Butyl dimethylsilyloxy)methyl)-N-(1-(3-(3-chloro-4-cyano phenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

Into a flask containing a solution of (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile (0.4 g, 17.5 mmol) in toluene (20 ml), 2 M solution of trimethyl aluminium in heptane (2.62 ml, 52.6 mmol) was added at 0° C. The resulting mixture was stirred at 0° C. for 10 min and a solution of methyl 2-((tert-butyldimethyl-silyloxy)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carboxylate (0.7 g, 17.5 mmol) in toluene (20 ml) was added at 0° C. The reaction mixture was heated at 110° C. for 4 h and diluted with water. The mixture was filtered through a celite bed and the filtrate was extracted with EtOAc. The organic layer was concentrated under reduced pressure. The product was purified by flash column chromatography. Yield 400 mg. 1H-NMR (400 MHz; DMSO-d6): δ −0.05 (s, 9H), 0.05 (s, 6H), 0.82-0.84 (s, 11H), 1.14 (d, 3H), 3.47 (t, 2H), 4.26-4.40 (m, 3H), 4.74 (s, 2H), 5.38 (s, 2H), 6.94 (d, 1H), 7.73 (s, 1H), 7.83 (d, 1H), 7.99 (d, 2H), 8.10 (d, 2H). LC-MS: [M+1]=629.38.

Workup

  1. additionwas added at 0° C
  2. temperatureThe reaction mixture was heated at 110° C. for 4 h
  3. filtrationThe mixture was filtered through a celite bed
  4. extractionthe filtrate was extracted with EtOAc
  5. concentrationThe organic layer was concentrated under reduced pressure
  6. customThe product was purified by flash column chromatography

Sources & evidence

ORD record
ord-a73fbbdfed974c8db5702f3fc80ee399
Source dataset
uspto-grants-2014_12
Patent number
US08921378B2

Reaction notes

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