Water → tert-butyl (2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)(3-methyl-5-nitropyridin-2-yl)carbamate

HRID 1039074Notes

Reaction equation

HRID 1039074 reaction equation
CC1C=CC(S(O[CH2:12][CH2:13][C@@H:14]2[CH2:16][C@@H:15]2[CH:17]2[CH2:22][CH2:21][N:20]([C:23]3[N:28]=[CH:27][C:26]([Cl:29])=[CH:25][N:24]=3)[CH2:19][CH2:18]2)(=O)=O)=CC=1.[CH3:30][C:31]1[C:32]([NH:40][C:41](=[O:47])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[N:33][CH:34]=[C:35]([N+:37]([O-:39])=[O:38])[CH:36]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[Cl:29][C:26]1[CH:27]=[N:28][C:23]([N:20]2[CH2:19][CH2:18][CH:17]([C@H:15]3[CH2:16][C@H:14]3[CH2:13][CH2:12][N:40]([C:32]3[C:31]([CH3:30])=[CH:36][C:35]([N+:37]([O-:39])=[O:38])=[CH:34][N:33]=3)[C:41](=[O:47])[O:42][C:43]([CH3:44])([CH3:45])[CH3:46])[CH2:22][CH2:21]2)=[N:24][CH:25]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 67962193Tert-butyl (3-methyl-5-nitropyridin-2-yl)carbamateHCID 866661412-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl 4-methylbenzenesulfonate

Product 1

HCID 67962326tert-butyl (2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)(3-methyl-5-nitropyridin-2-yl)carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl 4-methylbenzenesulfonate (95 mg, 0.22 mmol) from Step 1 of Example 2 and tert-butyl (3-methyl-5-nitropyridin-2-yl)carbamate (55 mg, 0.22 mmol) were added in DMF (2.2 mL), then cesium carbonate (212 mg, 0.65=101) was added and the reaction was heated to 50° C. overnight. The reaction was cooled to room temperature, water (20 mL) was added and extracted with ethyl acetate (50 mL), second wash with brine (20 mL). The organic phase was dried by magnesium sulfate, filtered, concentrated and purified by column chromatography through a 25 gram Biotage SNAP KP-Sil™ silica gel cartridge eluting with 6.3% ethyl acetate/hexanes to give the title compound as a pale yellow sticky solid.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. extractionextracted with ethyl acetate (50 mL)
  3. washsecond wash with brine (20 mL)
  4. dry with materialThe organic phase was dried by magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by column chromatography through a 25 gram Biotage SNAP KP-Sil™ silica gel cartridge
  8. washeluting with 6.3% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-cc3d5011be624a4399b9e5e4ef1b4905
Source dataset
uspto-grants-2013_10
Patent number
US08552022B2

Reaction notes

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