Aniline → HCID 58504455, compound

HRID 2367518Notes

Reaction equation

HRID 2367518 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.[NH2:61][C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=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:61][C:62]4[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=4)=[O:26])[CH2:18]3)[CH:10]=2)=[CH:5][C:4]=1[F:27])#[N:2]

Participants

7

Reactant 4

HCID 6115Aniline2×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 58504455HCID 58504455, compoundYield 94%

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 (300 mg, 0.81 mmol), HATU (340 mg, 0.89 mmol), and Hünig's base (0.21 mL, 1.20 mmol) in DMF (5 mL) was stirred at room temperature for 10 minutes. Aniline (0.085 mL, 0.93 mmol) was then added, and stirring continued at room temperature for 17 hours. LC-MS indicated about 50% conversion, so another portion each of Hünig's base (0.21 mL, 1.20 mmol) and HATU (340 mg, 0.89 mmol) were added. After about 10 minutes more aniline (0.085 mL, 0.93 mmol) was added, and the mixture was stirred for an additional 1.5 hours. It was 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, 10-35% EtOAc in hexanes gradient) to give the title compound (340 mg, about 80% purity) as a yellow oil. LC-MS (ES) m/z=447 [M+H]+.

Workup

  1. stirringstirring
  2. waitcontinued at room temperature for 17 hours
  3. stirringthe mixture was stirred for an additional 1.5 hours
  4. washwashed successively with water, saturated aqueous NaHCO3, and brine (25 mL each)
  5. dry with materialThe organic phase was then dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography (40 g SiO2, 10-35% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-80366fa4876440749e08587032dfb2fb
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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