Imidazole → HCID 86695107, compound

HRID 1503928Notes

Reaction equation

HRID 1503928 reaction equation
[I:1]I.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N1C=CN=C1.O[CH:28]([C:58]1[O:59][CH:60]=[CH:61][N:62]=1)[CH2:29][C@H:30]1[CH2:41][CH2:40][C:39]2[S:38][C:37]3[N:36]=[CH:35][N:34]=[C:33]([O:42][CH:43]4[CH2:48][CH2:47][CH:46]([N:49]([CH3:57])[C:50](=[O:56])[O:51][C:52]([CH3:55])([CH3:54])[CH3:53])[CH2:45][CH2:44]4)[C:32]=3[C:31]1=2>ClCCl>[I:1][CH:28]([C:58]1[O:59][CH:60]=[CH:61][N:62]=1)[CH2:29][C@H:30]1[CH2:41][CH2:40][C:39]2[S:38][C:37]3[N:36]=[CH:35][N:34]=[C:33]([O:42][CH:43]4[CH2:48][CH2:47][CH:46]([N:49]([CH3:57])[C:50](=[O:56])[O:51][C:52]([CH3:53])([CH3:54])[CH3:55])[CH2:45][CH2:44]4)[C:32]=3[C:31]1=2

Participants

6

Reactant 4

HCID 795ImidazoleHCID 807IodineHCID 11776TriphenylphosphineHCID 68115576HCID 68115576, compound

Product 1

HCID 86695107HCID 86695107, compoundYield 61.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

For the preparation of the starting material compound 47.1, see Example 47. A solution of iodine (244 mg), Ph3P (252 mg) and imidazole (143 mg, 2.10 mmol, 3.49 equiv) in dry dichloromethane (20 mL) was stirred at 0° C. for 30 min under nitrogen. Then a solution of tert-butyl N-(4-[[(3R)-3-[2-hydroxy-2-(1,3-oxazol-2-yl)ethyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate (310 mg, 0.60 mmol, 1.00 equiv) was added dropwise to the reaction mixture and the resulting solution was stirred for 2.5 h at room temperature. The reaction was then quenched with saturated aqueous NaHSO3 and extracted with 2×30 mL of dichloromethane. The organic layers were combined and washed with brine, dried over anhydrous sodium sulfate. After concentrated in vacuo, the residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:1) to give tert-butyl N-(4-[[(3R)-3-[2-iodo-2-(1,3-oxazol-2-yl)ethyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate (230 mg, 61%) as a yellow solid. MS (ES): m/z 625 (M+H)+.

Workup

  1. customThe reaction was then quenched with saturated aqueous NaHSO3
  2. extractionextracted with 2×30 mL of dichloromethane
  3. washwashed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationAfter concentrated in vacuo

Sources & evidence

ORD record
ord-f6820fc2bb404022bf9241ea92b876cb
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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