1-Hydroxybenzotriazole → HCID 68414528, compound

HRID 220313

Reaction equation

HRID 220313 reaction equation
C1([C:7]2[N:8]=[C:9]([CH2:26][CH2:27][C:28]([OH:30])=O)[N:10]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)C=CC=CC=1.CCN(C(C)C)C(C)C.[CH:40]1[CH:41]=[CH:42][C:43]2N(O)N=N[C:44]=2[CH:45]=1.[CH3:50][NH:51][CH2:52][CH2:53][C:54]1([OH:68])[CH2:59][CH:58]2[CH2:60][CH2:61][CH:55]1[CH:56]=[C:57]2[C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1>C1COCC1.C(Cl)Cl.C(Cl)CCl>[C:44]1([C:7]2[N:8]=[C:9]([CH2:26][CH2:27][C:28]([N:51]([CH2:52][CH2:53][C@:54]3([OH:68])[CH2:59][C@H:58]4[CH2:60][CH2:61][C@@H:55]3[CH:56]=[C:57]4[C:62]3[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=3)[CH3:50])=[O:30])[N:10]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:23])[CH3:24])[C:11]=2[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:43]=[CH:42][CH:41]=[CH:40][CH:45]=1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 684143723-[4,5-diphenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-propionic acidHCID 68415512rac-(1R*,2R*,4R*)-2-(2-methylamino-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-ol

Product 1

HCID 68414528HCID 68414528, compoundYield 91.9%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

145 mg of 3-[4,5-diphenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-propionic acid were dissolved in THF (0.13 mL)/DCM (0.5 mL). 0.160 mL of DIPEA, 50 mg of HOBt and 71 mg of EDC were added sequentially at rt. The reaction mixture was stirred for 5 min then 80 mg of rac-(1R*,2R*,4R*)-2-(2-methylamino-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-ol were added at rt. The reaction mixture was stirred on at rt then diluted with DCM and washed with sat.-NaHCO3 and brine. The organic phase was dried over anh. Na2SO4, filtered and concentrated in vacuo. The resulting crude material was purified by CC using EtOAc/MeOH/NEt3 as eluant from 100/0/1 to 95/5/1 to yield 189 mg of rac-3-[4,5-diphenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-N-[2-((1R*,2R*,4R*)-2-hydroxy-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl)-ethyl]-N-methyl-propionamide as a yellow oil.

Workup

  1. stirringThe reaction mixture was stirred on at rt
  2. washwashed with sat.-NaHCO3 and brine
  3. dry with materialThe organic phase was dried over anh. Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting crude material was purified by CC

Sources & evidence

ORD record
ord-0dae70123d2048afbcb8e128730f1905
Source dataset
uspto-grants-2012_06
Patent number
US08202885B2

Linked notes

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