Sodium hydride → HCID 89691365, compound

HRID 1504090Notes

Reaction equation

HRID 1504090 reaction equation
[H-].[Na+].[CH3:3][N:4]([CH3:12])[C@H:5]1[CH2:10][CH2:9][C@H:8]([OH:11])[CH2:7][CH2:6]1.[Si:13]([O:20][CH2:21][CH2:22][C@@H:23]1[CH2:35][C:34]2[C:33]3[C:32](Cl)=[N:31][CH:30]=[N:29][C:28]=3[S:27][C:26]=2[CH2:25][CH2:24]1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]>O1CCCC1>[Si:13]([O:20][CH2:21][CH2:22][C@@H:23]1[CH2:35][C:34]2[C:33]3[C:32]([O:11][CH:8]4[CH2:9][CH2:10][CH:5]([N:4]([CH3:12])[CH3:3])[CH2:6][CH2:7]4)=[N:31][CH:30]=[N:29][C:28]=3[S:27][C:26]=2[CH2:25][CH2:24]1)([C:16]([CH3:19])([CH3:17])[CH3:18])([CH3:14])[CH3:15]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86695167HCID 86695167, compoundHCID 178484116HCID 178484116, compound

Product 1

HCID 89691365HCID 89691365, compoundYield 43.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

NaH (60% dispersion in mineral oil, 63 mg, 3.00 equiv) was treated with trans-4-(dimethylamino)cyclohexan-1-ol (104 mg, 0.73 mmol, 1.40 equiv) in distilled tetrahydrofuran (8 mL) at room temperature under nitrogen. After stirring for min, (12S)-12-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-3-chloro-8-thia-4,6-diazatricyclo[7.4.0.0[2,7]]trideca-1(9),2(7),3,5-tetraene (200 mg, 0.52 mmol, 1.00 equiv) was added and the resulting solution was stirred overnight at room temperature for 8 h. The reaction was then quenched with saturated aqueous NH4Cl and extracted with 3×50 mL of ethyl acetate. The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (4:1) to afford 4-[[(12S)-12-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-8-thia-4,6-diazatricyclo[7.4.0.0[2,7]]trideca-1(9),2(7),3,5-tetraen-3-yl]oxy]-N,N-dimethylcyclohexan-1-amine (110 mg, 43%) as a light yellow solid. MS (ES): m/z 490 (M+H)+.

Workup

  1. additionwas added
  2. customThe reaction was then quenched with saturated aqueous NH4Cl
  3. extractionextracted with 3×50 mL of ethyl acetate
  4. washwashed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-bcd16e14a995436787869564b34246cf
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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