Acetonitrile → HCID 178483726, compound

HRID 590387Notes

Reaction equation

HRID 590387 reaction equation
[Si]([O:8][C@H:9]([C:49]1[CH:58]=[CH:57][C:56]([OH:59])=[C:55]2[C:50]=1[CH:51]=[CH:52][C:53](=[O:60])[NH:54]2)[CH2:10][NH:11][CH2:12][C:13]1[CH:48]=[CH:47][C:16]2[N:17]([CH2:21][CH2:22][CH2:23][N:24]([CH3:46])[C@H:25]3[CH2:30][CH2:29][C@H:28]([O:31][C:32]([C:41]4[S:42][CH:43]=[CH:44][CH:45]=4)([C:36]4[S:37][CH:38]=[CH:39][CH:40]=4)[C:33]([O-:35])=[O:34])[CH2:27][CH2:26]3)[C:18](=[O:20])[NH:19][C:15]=2[CH:14]=1)(C(C)(C)C)(C)C.[FH:61].F.F.C(N(CC)CC)C.C(#N)C>C1COCC1>[FH:61].[FH:61].[OH:8][C@H:9]([C:49]1[CH:58]=[CH:57][C:56]([OH:59])=[C:55]2[C:50]=1[CH:51]=[CH:52][C:53](=[O:60])[NH:54]2)[CH2:10][NH:11][CH2:12][C:13]1[CH:48]=[CH:47][C:16]2[N:17]([CH2:21][CH2:22][CH2:23][N:24]([CH3:46])[C@H:25]3[CH2:30][CH2:29][C@H:28]([O:31][C:32]([C:36]4[S:37][CH:38]=[CH:39][CH:40]=4)([C:41]4[S:42][CH:43]=[CH:44][CH:45]=4)[C:33]([OH:35])=[O:34])[CH2:27][CH2:26]3)[C:18](=[O:20])[NH:19][C:15]=2[CH:14]=1

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 175505N,N-Diethylethanamine trihydrofluorideHCID 178483727HCID 178483727, compound2×

Product 1

HCID 178483726HCID 178483726, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

95 mg (0.12 mmol) of 71% pure trans-4-[{3-[5-({[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl]propyl}(methyl)amino]cyclohexylhydroxy(di-2-thienyl)acetate (Intermediate 17) are dissolved in 2 ml THF. 0.05 ml (0.31 mmol) of triethylamine trihydrofluoride are added and the system stirred overnight at room temperature. The supernatant is discarded and the residue is washed with 2×10 additional ml of THF and the supernatant is again discarded. Acetonitrile (5 ml) is added to the residue and the solid is stirred for 2 hr, aged overnight, filtered and washed with acetonitrile. The residue is chromatographically purified with C-18 reversed phase column silica from MERCK, using water to acetonitrile/MeOH as eluents with a gradient from 0% to 100%. 31.8 mg of pure title compound are thus obtained (51% yield).

Workup

  1. stirringthe solid is stirred for 2 hr, aged overnight
  2. filtrationfiltered
  3. washwashed with acetonitrile
  4. customThe residue is chromatographically purified with C-18

Sources & evidence

ORD record
ord-0b9556e327164deb9bea53f9632e0321
Source dataset
uspto-grants-2016_01
Patent number
US09233108B2

Reaction notes

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