Sodium hydride → (3R)-3-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-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-tetraene

HRID 1503932Notes

Reaction equation

HRID 1503932 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][C@H:11]1[CH2:22][CH2:21][C:20]2[S:19][C:18]3[N:17]=[CH:16][N:15]=[C:14](Cl)[C:13]=3[C:12]1=2)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].[N:26]1([C@H:32]2[CH2:37][CH2:36][C@H:35]([OH:38])[CH2:34][CH2:33]2)[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1>C1COCC1>[Si:1]([O:8][CH2:9][CH2:10][C@H:11]1[CH2:22][CH2:21][C:20]2[S:19][C:18]3[C:13](=[C:14]([O:38][CH:35]4[CH2:34][CH2:33][CH:32]([N:26]5[CH2:31][CH2:30][O:29][CH2:28][CH2:27]5)[CH2:37][CH2:36]4)[N:15]=[CH:16][N:17]=3)[C:12]1=2)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86695093(R)-5-(2-((Tert-butyldimethylsilyl)oxy)ethyl)-4-chloro-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-D]pyrimidine2×HCID 178521573HCID 178521573, compound

Product 1

HCID 86695110(3R)-3-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-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-tetraeneYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

For the preparation of the starting material compound 25.1, see Example 25. Sodium hydride (60% dispersion in mineral oil, 130 mg, 3.25 mmol, 4.00 equiv) was treated with trans-4-(morpholin-4-yl)cyclohexan-1-ol (192 mg, 1.04 mmol, 1.27 equiv) in freshly distilled THF (15 mL) at 0° C. under nitrogen. After stirring for 30 min at room temperature, then (3R)-3-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-12-chloro-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraene (300 mg, 0.81 mmol, 1.00 equiv) was added and the resulting solution was allowed to react, with stirring, for an additional 2 hr at room temperature. The reaction was then quenched with saturated aqueous NH4Cl, extracted with 3×20 mL of ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:8) to provide (3R)-3-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-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 (378 mg, 90%) as a yellow oil. MS (ES): m/z 518 [M+H]+.

Workup

  1. customto react
  2. stirringwith stirring, for an additional 2 hr at room temperature
  3. customThe reaction was then quenched with saturated aqueous NH4Cl
  4. extractionextracted with 3×20 mL of ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-1518daaf63034d17aef7a85e6ecb06b3
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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