Sodium hydride → HCID 86695127, compound

HRID 1503959Notes

Reaction equation

HRID 1503959 reaction equation
[N:1]1([C@H:7]2[CH2:12][CH2:11][C@H:10]([OH:13])[CH2:9][CH2:8]2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[H-].[Na+].[Si:16]([O:23][CH2:24][CH:25]1[CH2:36][CH2:35][C:34]2[S:33][C:32]3[C:27](=[C:28](Cl)[N:29]=[CH:30][N:31]=3)[C:26]1=2)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]>C1COCC1>[Si:16]([O:23][CH2:24][CH:25]1[CH2:36][CH2:35][C:34]2[S:33][C:32]3[C:27](=[C:28]([O:13][CH:10]4[CH2:9][CH2:8][CH:7]([N:1]5[CH2:2][CH2:3][O:4][CH2:5][CH2:6]5)[CH2:12][CH2:11]4)[N:29]=[CH:30][N:31]=3)[C:26]1=2)([C:19]([CH3:22])([CH3:20])[CH3:21])([CH3:18])[CH3:17]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86695128HCID 86695128, compoundHCID 178521573HCID 178521573, compound

Product 1

HCID 86695127HCID 86695127, compoundYield 69.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

For the preparation of the starting material compound 65.1, please refer to the experimental procedure for Example 65. To a solution of trans-4-(morpholin-4-yl)cyclohexan-1-ol (277 mg, 1.50 mmol, 1.50 equiv) in distilled THF (20 mL) was added sodium hydride (605 dispersion in mineral oil, 200 mg, 5.00 mmol, 5.00 equiv) slowly at 0° C. under nitrogen. After stirring for 30 min at room temperature, a solution of 3-[[(tert-butyldimethylsilyl)oxy]methyl]-12-chloro-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraene (355 mg, 1.00 mmol, 1.00 equiv) in 5 mL of THF was added dropwise and the resulting solution was stirred for 6 h at ambient temperature. The reaction was quenched with NH4Cl (sat.), extracted with EtOAc (3×80 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate. After filtration and concentration in vacuo, the residue was purified by a silica gel column with EtOAc/petroleum ether (1:1-3:1) to provide 350 mg (69%) of the title 3-[[(tert-butyldimethylsilyl)oxy]methyl]-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 as a light yellow oil. MS: (ES, m/z): 504 [M+H]+.

Workup

  1. stirringthe resulting solution was stirred for 6 h at ambient temperature
  2. customThe reaction was quenched with NH4Cl (sat.)
  3. extractionextracted with EtOAc (3×80 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationAfter filtration and concentration in vacuo
  7. customthe residue was purified by a silica gel column with EtOAc/petroleum ether (1:1-3:1)

Sources & evidence

ORD record
ord-336942a5bd31401f8c60a62f3bf7f45f
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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