Triethylamine → HCID 86695138, compound

HRID 1503975Notes

Reaction equation

HRID 1503975 reaction equation
[OH:1][CH2:2][CH2:3][C@H:4]1[CH2:15][CH2:14][C:13]2[S:12][C:11]3[N:10]=[CH:9][N:8]=[C:7]([O:16][CH:17]4[CH2:22][CH2:21][CH:20]([N:23]([CH3:32])[CH2:24][C:25]([N:27]5[CH2:31][CH2:30][CH2:29][CH2:28]5)=[O:26])[CH2:19][CH2:18]4)[C:6]=3[C:5]1=2.[CH3:33][S:34](Cl)(=[O:36])=[O:35].C(N(CC)CC)C>CN(C=O)C>[CH3:33][S:34]([O:1][CH2:2][CH2:3][C@H:4]1[CH2:15][CH2:14][C:13]2[S:12][C:11]3[N:10]=[CH:9][N:8]=[C:7]([O:16][CH:17]4[CH2:18][CH2:19][CH:20]([N:23]([CH3:32])[CH2:24][C:25](=[O:26])[N:27]5[CH2:28][CH2:29][CH2:30][CH2:31]5)[CH2:21][CH2:22]4)[C:6]=3[C:5]1=2)(=[O:36])=[O:35]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 68115499HCID 68115499, compound

Product 1

HCID 86695138HCID 86695138, compoundYield 90.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

For the preparation of the starting material Compound I-90, please refer to Example 107. A 25-mL round-bottom flask, purged and maintained with an inert atmosphere of nitrogen, was charged with a solution of 2-[(4-[[(3R)-3-(2-hydroxyethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)(methyl)amino]-1-(pyrrolidin-1-yl)ethan-1-one (100 mg, 0.22 mmol, 1.00 equiv) in 5 mL of distilled DMF. MsCl (38 mg, 0.33 mmol, 1.50 equiv) and triethylamine (66.7 mg, 0.66 mmol, 3.00 equiv) were added at 0° C. The resulting solution was stirred overnight at room temperature. The reaction was then quenched with water, extracted with DCM. The organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by column chromatography on silica gel with DCM/MeOH (20:1 to 10:1) to give 2-[(3R)-12-[(4-[methyl[2-oxo-2-(pyrrolidin-1-yl)ethyl]amino]cyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]ethyl methanesulfonate (107 mg) as a white solid. MS (ES): m/z 537 [M+H]+.

Workup

  1. customFor the preparation of the starting material Compound
  2. customA 25-mL round-bottom flask, purged
  3. temperaturemaintained with an inert atmosphere of nitrogen
  4. customThe reaction was then quenched with water
  5. extractionextracted with DCM
  6. washThe organic phase was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified by column chromatography on silica gel with DCM/MeOH (20:1 to 10:1)

Sources & evidence

ORD record
ord-ce3f45622d9445d4a53217513a53587d
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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