Diethyl Ether → HCID 123772918, compound

HRID 1056992Notes

Reaction equation

HRID 1056992 reaction equation
C[Mg]I.[CH2:4](OCC)C.[F:9][C:10]1[CH:47]=[C:46]([F:48])[CH:45]=[CH:44][C:11]=1[O:12][C:13]1[C:21]2[N:20]=[CH:19][N:18]([CH3:22])[C:17]=2[C:16]([CH:23]=[O:24])=[CH:15][C:14]=1[C:25]1[C:26]2[CH:35]=[N:34][N:33]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[C:27]=2[C:28](=[O:32])[N:29]([CH3:31])[CH:30]=1>O1CCCC1>[F:9][C:10]1[CH:47]=[C:46]([F:48])[CH:45]=[CH:44][C:11]=1[O:12][C:13]1[C:21]2[N:20]=[CH:19][N:18]([CH3:22])[C:17]=2[C:16]([CH:23]([OH:24])[CH3:4])=[CH:15][C:14]=1[C:25]1[C:26]2[CH:35]=[N:34][N:33]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:41])([CH3:42])[CH3:43])[C:27]=2[C:28](=[O:32])[N:29]([CH3:31])[CH:30]=1

Participants

5

Reactant 3

HCID 3283Diethyl Ether2×HCID 123895025HCID 123895025, compoundHCID 178418373HCID 178418373, compound2×

Product 1

HCID 123772918HCID 123772918, compoundYield 68.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A 3.0 M solution of methylmagnesium iodide in diethyl ether (21.1 μL, 0.0634 mmol) was added to a solution of 4-(2,4-difluorophenoxy)-1-methyl-5-(6-methyl-7-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-6,7-dihydro-1H-pyrazolo[3,4-c]pyridin-4-yl)-1H-benzimidazole-7-carbaldehyde (0.0478 g, 0.0845 mmol) in tetrahydrofuran (0.734 mL) at 0° C. The resultant reaction mixture was stirred at 0° C. for 1 h, after which time an additional amount of 3.0 M solution of methylmagnesium iodide in diethyl ether (42.2 μL, 0.127 mmol) was added to the reaction mixture and stirring was continued at 0° C. for 30 min. The reaction mixture was quenched at 0° C. with methanol, diluted with methanol, and purified via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (25.2 mg, 51%). LCMS calculated for C29H34F2N5O4Si (M+H)+: m/z=582.2. found: 582.2.

Workup

  1. customThe resultant reaction mixture
  2. stirringstirring
  3. waitwas continued at 0° C. for 30 min
  4. customThe reaction mixture was quenched at 0° C. with methanol
  5. additiondiluted with methanol
  6. custompurified via preparative LCMS (XBridge C18 column
  7. washeluting with a gradient of acetonitrile/water 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-b1e029abb5f64c5a97cc43dd2049ebec
Source dataset
uspto-grants-2016_07
Patent number
US09399640B2

Reaction notes

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