N-methyl-2-pyrrolidone → HCID 178496462, compound

HRID 1852548Notes

Reaction equation

HRID 1852548 reaction equation
CS([C:5]1[N:10]=[C:9]([N:11]2[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=3[N:13]=[N:12]2)[CH:8]=[CH:7][N:6]=1)(=O)=O.CN1C(=O)CCC1.C(N(C(C)C)CC)(C)C.[NH2:36][CH:37]1[CH2:42][CH2:41][CH:40]([NH:43][C:44](=[O:48])[CH2:45][O:46][CH3:47])[CH2:39][CH2:38]1>C(Cl)Cl.CCOC(C)=O.CCCCCC.O>[N:11]1([C:9]2[CH:8]=[CH:7][N:6]=[C:5]([NH:36][C@H:37]3[CH2:42][CH2:41][C@H:40]([NH:43][C:44](=[O:48])[CH2:45][O:46][CH3:47])[CH2:39][CH2:38]3)[N:10]=2)[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:13]=[N:12]1

Participants

9

Reactant 4

HCID 13387N-methyl-2-pyrrolidone2×HCID 81531DiisopropylethylamineHCID 59718913HCID 59718913, compound2×HCID 61279804HCID 61279804, compound2×

Product 1

HCID 178496462HCID 178496462, compoundYield 63%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a 10 mL sealable tube loaded with 1-(2-methanesulfonyl-pyrimidin-4-yl)-1H-benzotriazole (99.1 mg, 0.36 mmol) were added NMP (1 mL) and diisopropylethylamine (0.19 mL, 1.09 mmol). To a second 5 mL sealable tube loaded with N-(4-amino-cyclohexyl)-2-methoxy-acetamide (100 mg, 0.36 mmol) was added NMP (1 mL). Both tubes were heated at 120° C. and at complete dissolution of the solids the solution of 1-(2-methanesulfonyl-pyrimidin-4-yl)-1H-benzotriazole was transferred via cannula into the tube containing the solution of N-(4-amino-cyclohexyl)-2-methoxy-acetamide. The resulting mixture was stirred for 1.5 hours at 120° C., then cooled to RT and poured into water (15 mL). The resulting mixture was stirred overnight, then diluted with DCM and washed with water. The aqueous layer was separated and extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to give an oil which was dissolved in a small amount of EtOAc and hexane was added to precipitate the solids. The resulting mixture was allowed to settle for 1 h, after which the liquid supernatant was carefully decanted away. The remaining solid was dried under reduced pressure to yield 86 mg (63% yield) of trans-N-[4-(4-benzotriazol-1-yl-pyrimidin-2-ylamino)-cyclohexyl]-2-methoxy-acetamide. MS=381 [M+H]+; MP=233.5-235.4° C.

Workup

  1. temperaturecooled to RT
  2. stirringThe resulting mixture was stirred overnight
  3. washwashed with water
  4. customThe aqueous layer was separated
  5. extractionextracted with DCM
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give an oil which
  10. additionwas added
  11. customto precipitate the solids
  12. waitto settle for 1 h
  13. customafter which the liquid supernatant was carefully decanted away
  14. customThe remaining solid was dried under reduced pressure

Sources & evidence

ORD record
ord-d8ce62c3551f4f4bb70ded0bb05c5393
Source dataset
uspto-grants-2015_02
Patent number
US08962622B2

Reaction notes

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