Imidazole → HCID 86695131, compound

HRID 1503963Notes

Reaction equation

HRID 1503963 reaction equation
[OH:1][CH:2]([CH2:5][C@H:6]1[CH2:17][CH2:16][C:15]2[S:14][C:13]3[N:12]=[CH:11][N:10]=[C:9]([O:18][CH:19]4[CH2:24][CH2:23][CH:22]([N:25]5[CH2:30][CH2:29][O:28][CH2:27][CH2:26]5)[CH2:21][CH2:20]4)[C:8]=3[C:7]1=2)[C:3]#[N:4].[CH3:31][C:32]([Si:35](Cl)([CH3:37])[CH3:36])([CH3:34])[CH3:33].N1C=CN=C1>ClCCl.CN(C)C1C=CN=CC=1.O>[Si:35]([O:1][CH:2]([CH2:5][C@H:6]1[CH2:17][CH2:16][C:15]2[S:14][C:13]3[N:12]=[CH:11][N:10]=[C:9]([O:18][CH:19]4[CH2:20][CH2:21][CH:22]([N:25]5[CH2:30][CH2:29][O:28][CH2:27][CH2:26]5)[CH2:23][CH2:24]4)[C:8]=3[C:7]1=2)[C:3]#[N:4])([C:32]([CH3:34])([CH3:33])[CH3:31])([CH3:37])[CH3:36]

Participants

7

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 86695132HCID 86695132, compound

Product 1

HCID 86695131HCID 86695131, compoundYield 95%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A 100-mL round-bottom flask was charged with a solution of 2-hydroxy-3-[(3R)-12-[[4-(morpholin-4-yl)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]propanenitrile (290 mg, 0.68 mmol, 1.00 equiv) in dichloromethane (10 mL). TBSCl (153 mg, 1.02 mmol, 1.51 equiv), imidazole (92 mg, 1.35 mmol, 2.00 equiv) and 4-dimethylaminopyridine (17 mg, 0.14 mmol, 0.21 equiv) were added successively at 0° C. under nitrogen. The resulting mixture was stirred overnight at room temperature. After completion, the resulting solution was diluted with water, extracted with 3×30 mL of dichloromethane, dried over sodium sulfate and concentrated under vacuum. The residue was purified by column chromatography on silica gel with ethyl acetate/petroleum ether (1:1) to afford the desired 2-[(tert-butyldimethylsilyl)oxy]-3-[(3R)-12-[[4-(morpholin-4-yl)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2 (6),9,11-tetraen-3-yl]propanenitrile (350 mg, 95%) as a yellow oil. MS (ES): m/z 543 [M+H]+.

Workup

  1. extractionextracted with 3×30 mL of dichloromethane
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified by column chromatography on silica gel with ethyl acetate/petroleum ether (1:1)

Sources & evidence

ORD record
ord-6e2b5af49baa4315882a27da2a82e3dd
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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