Isopropyl Acetate → HCID 89614920, compound

HRID 2177867Notes

Reaction equation

HRID 2177867 reaction equation
F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[CH3:34][NH:35][C:36]1[N:41]=[C:40]([C:42]2[NH:43][C:44]3[C:49]([CH:50]=2)=[CH:48][C:47]([C:51]([OH:53])=O)=[CH:46][CH:45]=3)[CH:39]=[CH:38][N:37]=1.[CH3:54][O:55][C:56](=[O:73])[C@@H:57]([NH2:72])[CH2:58][N:59]([C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1)[C:60]1[N:65]=[CH:64][CH:63]=[CH:62][N:61]=1.C(=O)([O-])O.[Na+].C(OC(C)C)(=O)C>CN(C)C=O>[CH3:54][O:55][C:56](=[O:73])[C@@H:57]([NH:72][C:51]([C:47]1[CH:48]=[C:49]2[C:44](=[CH:45][CH:46]=1)[NH:43][C:42]([C:40]1[CH:39]=[CH:38][N:37]=[C:36]([NH:35][CH3:34])[N:41]=1)=[CH:50]2)=[O:53])[CH2:58][N:59]([C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1)[C:60]1[N:61]=[CH:62][CH:63]=[CH:64][N:65]=1

Participants

8

Reactant 6

HCID 7915Isopropyl AcetateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12147834HCID 12147834, compoundHCID 89615082HCID 89615082, compound

Product 1

HCID 89614920HCID 89614920, compoundYield 51.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

4.01 g (10.6 mmol) of N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)-uronium hexafluorophosphate and 6.82 g (52.8 mmol) of diisopropylethylamine were added to a solution of 2.36 g (8.80 mmol) of 2-(2-methylaminopyrimidin-4-yl)-1H-indole-5-carboxylic acid in 80 ml of dimethylformamide under cooling with an ice bath, and the mixture was stirred at 0° C. for 1.5 h. Then a solution of 2.40 g (8.80 mmol) of (S)-2-amino-3-(phenyl-pyrimidin-2-yl-amino)propionic acid methyl ester (98.9% ee (enantiomeric excess)) in 22 ml of dimethylformamide was added. The mixture was stirred for 2 h, and then an aqueous solution of sodium hydrogencarbonate and isopropyl acetate were added. The organic phase was separated, washed with a saturated solution of sodium chloride and concentrated in vacuo. The solid that precipitated was filtered off with suction, dried in vacuo and purified by column chromatography (silica gel, dichloromethane:methanol (25:1)). 2.35 g (50%) of (S)-2-{[2-(2-methylaminopyrimidin-4-yl)-1H-indole-5-carbonyl]amino}-3-(phenyl-pyrimidin-2-yl-amino)propionic acid methyl ester were obtained as a yellowish solid.

Workup

  1. temperatureunder cooling with an ice bath
  2. stirringThe mixture was stirred for 2 h
  3. customThe organic phase was separated
  4. washwashed with a saturated solution of sodium chloride
  5. concentrationconcentrated in vacuo
  6. customThe solid that precipitated
  7. filtrationwas filtered off with suction
  8. customdried in vacuo
  9. custompurified by column chromatography (silica gel, dichloromethane:methanol (25:1))

Sources & evidence

ORD record
ord-e5e7fedd9ec9426c8df5a0e38af103b7
Source dataset
uspto-grants-2015_06
Patent number
US09067918B2

Reaction notes

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