Sodium hydride → tert-butyl N-(4-[[(3R)-3-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-ethylcarbamate

HRID 1503954Notes

Reaction equation

HRID 1503954 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].[CH2:24]([N:26]([CH:34]1[CH2:39][CH2:38][CH:37]([OH:40])[CH2:36][CH2:35]1)[C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH3:25].[H-].[Na+]>O1CCCC1>[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]([O:40][CH:37]4[CH2:38][CH2:39][CH:34]([N:26]([CH2:24][CH3:25])[C:27](=[O:33])[O:28][C:29]([CH3:30])([CH3:31])[CH3:32])[CH2:35][CH2:36]4)[C:13]=3[C:12]1=2)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 681155081,1-Dimethylethyl N-ethyl-N-(trans-4-hydroxycyclohexyl)carbamate2×HCID 86695093(R)-5-(2-((Tert-butyldimethylsilyl)oxy)ethyl)-4-chloro-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-D]pyrimidine2×

Product 1

HCID 86695126tert-butyl N-(4-[[(3R)-3-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-ethylcarbamateYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

For the preparation of the starting material compound 25.1, please refer to the experimental procedure for the synthesis of compound Example 25. To a solution of tert-butyl N-ethyl-N-(4-hydroxycyclohexyl)carbamate (intermediate 101.5, 322.68 mg, 1.33 mmol, 1.22 equiv) in distilled tetrahydrofuran (10 mL) was added sodium hydride (151.76 mg) slowly at 0° C. and the reaction mixture was stirred at room temperature for 30 min. Then (3R)-3-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-12-chloro-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraene (400 mg, 1.08 mmol, 1.00 equiv) in THF (5 mL) was added to the mixture via syringe and the resulting solution was stirred for 3 hr at ambient temperature. The reaction was then quenched by the addition of 40 mL of saturated aqueous NH4Cl and extracted with 3×80 mL of ethyl acetate. The combined organic layers were combined, 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 (1:5) to afford tert-butyl N-(4-[[(3R)-3-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-ethylcarbamate (570 mg, 91%) as a colorless oil. MS (ES): m/z 576 [M+H]+.

Workup

  1. customplease refer to the experimental procedure for the synthesis of compound Example 25
  2. stirringthe resulting solution was stirred for 3 hr at ambient temperature
  3. customThe reaction was then quenched by the addition of 40 mL of saturated aqueous NH4Cl
  4. extractionextracted with 3×80 mL of ethyl acetate
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-10d9b92af75c4e15935e9ef11725eb29
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

Loading…