Imidazole → HCID 77412678, compound

HRID 1503961Notes

Reaction equation

HRID 1503961 reaction equation
[N:1]1([CH:7]2[CH2:12][CH2:11][CH:10]([O:13][C:14]3[N:15]=[CH:16][N:17]=[C:18]4[C:25]=3[C:24]3[CH:23]([CH2:26]O)[CH2:22][CH2:21][C:20]=3[S:19]4)[CH2:9][CH2:8]2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.N1C=CN=C1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[I:52]I>C(Cl)Cl>[I:52][CH2:26][CH:23]1[CH2:22][CH2:21][C:20]2[S:19][C:18]3[C:25](=[C:14]([O:13][CH:10]4[CH2:11][CH2:12][CH:7]([N:1]5[CH2:6][CH2:5][O:4][CH2:3][CH2:2]5)[CH2:8][CH2:9]4)[N:15]=[CH:16][N:17]=3)[C:24]1=2

Participants

6

Reactant 4

HCID 795ImidazoleHCID 807IodineHCID 11776TriphenylphosphineHCID 86695129HCID 86695129, compound

Product 1

HCID 77412678HCID 77412678, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A 20-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen was charged with a solution of (12-[[4-(morpholin-4-yl)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-3-yl)methanol (260 mg, 0.67 mmol, 1.00 equiv) in DCM (20 mL). Imidazole (91 mg, 1.34 mmol, 2.00 equiv) and PPh3 (264 mg, 1.01 mmol, 1.50 equiv) were added successively, followed by the addition of I2 (255 mg, 1.00 mmol, 1.50 equiv) at room temperature. The resulting solution was stirred overnight at ambient temperature and diluted with DCM and washed with Na2SO3 (sat.) and brine. The organic layer was dried over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was purified by a silica gel column with EtOAc/petroleum ether (1:1-3:1) to provide the desired 3-(iodomethyl)-12-[[4-(morpholin-4-yl)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraene (287 mg, 86%) as a light yellow solid. MS (ES): m/z 500 [M+H]+.

Workup

  1. customA 20-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. washwashed with Na2SO3 (sat.) and brine
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationAfter filtration and concentration under reduced pressure
  6. customthe residue was purified by a silica gel column with EtOAc/petroleum ether (1:1-3:1)

Sources & evidence

ORD record
ord-c314c0f030d2478b91d467a10e1d2732
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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