Cyclohexylamine → HCID 58504801, compound

HRID 2367520Notes

Reaction equation

HRID 2367520 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([NH:15][CH3:16])[N:12]=[C:11]([N:17]3[C@H:22]([CH3:23])[CH2:21][O:20][C@H:19]([C:24]([OH:26])=O)[CH2:18]3)[CH:10]=2)=[CH:5][C:4]=1[F:27])#[N:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH:61]1([NH2:67])[CH2:66][CH2:65][CH2:64][CH2:63][CH2:62]1>CN(C=O)C.CCOC(C)=O>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([NH:15][CH3:16])[N:12]=[C:11]([N:17]3[C@H:22]([CH3:23])[CH2:21][O:20][C@H:19]([C:24]([NH:67][CH:61]4[CH2:66][CH2:65][CH2:64][CH2:63][CH2:62]4)=[O:26])[CH2:18]3)[CH:10]=2)=[CH:5][C:4]=1[F:27])#[N:2]

Participants

7

Reactant 4

HCID 7965Cyclohexylamine2×HCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 51353729HCID 51353729, compound

Product 1

HCID 58504801HCID 58504801, compoundYield 89.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (2S,5R)-4-[6-(4-cyano-3-fluorophenyl)-2-(methylamino)-4-pyrimidinyl]-5-methyl-2-morpholinecarboxylic acid (302 mg, 0.81 mmol), HATU (343 mg, 0.90 mmol), and Hünig's base (0.21 mL, 1.20 mmol) in DMF (5 mL) was stirred at room temperature for 10 minutes. Cyclohexylamine (0.105 mL, 0.92 mmol) was then added and stirring continued at room temperature for 17 hours. LC-MS indicated abot 50% conversion so another portion each of Hünig's base (0.21 mL, 1.20 mmol) and HATU (343 mg, 0.90 mmol) were added. After about 10 minutes more cyclohexylamine (0.105 mL, 0.92 mmol) was added, and the mixture was stirred for an additional 1.5 hours, then diluted with EtOAc (25 mL) and washed successively with water, saturated aqueous NaHCO3, and brine (25 mL each). The organic phase was then dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (40 g SiO2, 10-40% EtOAc in hexanes gradient) to give the title compound (328 mg) as a yellow oil. LC-MS (ES) m/z=453 [M+H]+.

Workup

  1. stirringstirring
  2. waitcontinued at room temperature for 17 hours
  3. additionwere added
  4. stirringthe mixture was stirred for an additional 1.5 hours
  5. washwashed successively with water, saturated aqueous NaHCO3, and brine (25 mL each)
  6. dry with materialThe organic phase was then dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography (40 g SiO2, 10-40% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-0e499124074e4516acdf23160f698b03
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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