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]-1-ethylcyclohexyl)carbamate

HRID 1503972Notes

Reaction equation

HRID 1503972 reaction equation
[H-].[Na+].[CH2:3]([C:5]1([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:10][CH2:9][CH:8]([OH:11])[CH2:7][CH2:6]1)[CH3:4].[Si:20]([O:27][CH2:28][CH2:29][C@H:30]1[CH2:41][CH2:40][C:39]2[S:38][C:37]3[N:36]=[CH:35][N:34]=[C:33](Cl)[C:32]=3[C:31]1=2)([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21]>C1COCC1>[Si:20]([O:27][CH2:28][CH2:29][C@H:30]1[CH2:41][CH2:40][C:39]2[S:38][C:37]3[N:36]=[CH:35][N:34]=[C:33]([O:11][CH:8]4[CH2:9][CH2:10][C:5]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])([CH2:3][CH3:4])[CH2:6][CH2:7]4)[C:32]=3[C:31]1=2)([C:23]([CH3:26])([CH3:24])[CH3:25])([CH3:22])[CH3:21]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 68110282tert-butyl N-(1-ethyl-4-hydroxycyclohexyl)carbamateHCID 86695093(R)-5-(2-((Tert-butyldimethylsilyl)oxy)ethyl)-4-chloro-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-D]pyrimidine

Product 1

HCID 86695137tert-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]-1-ethylcyclohexyl)carbamateYield 47.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
18 °C

Procedure

Sodium hydride (605 dispersion in mineral oil, 283 mg, 7.08 mmol, 3.65 equiv) was treated with tert-butyl N-(1-ethyl-4-hydroxycyclohexyl)carbamate (430 mg, 1.77 mmol, 0.91 equiv) in 50 mL of distilled THF at room temperature for 30 mins. Then a solution of (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 (25.1, 716 mg, 1.94 mmol, 1.00 equiv) in THF (5 mL) was added dropwise and the resulting solution was stirred for 14 hr at 18° C. The reaction was then quenched with saturated aqueous NH4Cl and extracted with 3×50 mL of ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5) to afford the corresponding 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]-1-ethylcyclohexyl)carbamate (480 mg, 43%) as a colorless oil. MS: 576 [M+H]+.

Workup

  1. customThe reaction was then quenched with saturated aqueous NH4Cl
  2. extractionextracted with 3×50 mL of ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7bd856b416174467872b03922e4a4b14
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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