Diisopropylethylamine → HCID 118061845, compound

HRID 575530Notes

Reaction equation

HRID 575530 reaction equation
Cl.[Cl:2][C:3]1[N:8]=[C:7]([CH3:9])[N:6]=[C:5]([NH2:10])[C:4]=1[CH2:11][CH2:12][CH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.CN(C(=[N+](C)C)ON1C2=NC=CC=C2N=N1)C.[C:52]([O:56][C:57]([NH:59][C@@H:60]([CH3:64])[C:61](O)=[O:62])=[O:58])([CH3:55])([CH3:54])[CH3:53]>CN(C=O)C>[NH2:10][C:5]1[C:4]([CH2:11][CH2:12][CH:13]2[CH2:18][CH2:17][N:16]([C:61](=[O:62])[C@@H:60]([NH:59][C:57](=[O:58])[O:56][C:52]([CH3:54])([CH3:53])[CH3:55])[CH3:64])[CH2:15][CH2:14]2)=[C:3]([Cl:2])[N:8]=[C:7]([CH3:9])[N:6]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 85082Tert-butoxycarbonylalanineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118061513HCID 118061513, compound

Product 1

HCID 118061845HCID 118061845, compoundYield 153.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into each of two round bottom flasks add 6-chloro-2-methyl-5-[2-(4-piperidyl)ethyl]pyrimidin-4-amine hydrochloride (12.50 g, 42.92 mmol), diisopropylethylamine (22.46 mL, 128.7 mmol) and DMF (100 mL). Cool the two mixtures in a cold water bath and stir for 5 min. Add to each of the mixtures [dimethylamino(triazolo[4,5-b]pyridin-3-yloxy)methylene]-dimethyl-ammonium hexafluorophosphate (17.95 g, 47.21 mmol) and (2S)-2-(tert-butoxycarbonylamino)propanoic acid (8.93 g, 47.21 mmol) in one portion. Stir the mixtures at RT for 90 min Pour the mixtures into separate separatory funnels along with water (300 mL) and EtOAc (400 mL), shake and partition. Extract the aqueous layers with EtOAc (3×300 mL), wash the respective organic layers with water (4×250 mL), saturated aqueous NaCl (200 mL) and dry over MgSO4, filter and concentrate under reduced pressure. Purify the combined materials via silica gel chromatography eluting with 70% to 100% EtOAc in hexanes. Combine and concentrate the purified fractions under reduced pressure. Dilute the residue with EtOAc (500 mL) and wash with saturated aqueous NH4Cl (100 mL), saturated aqueous NaHCO3 (100 mL), water (100 mL) and saturated aqueous NaCl (100 mL). Dry the organics over MgSO4, filter, and concentrate under reduced pressure to give the title compound as a white solid (28.00 g, 76%). LC-ES/MS m/z (35Cl/37Cl) 426.2/428.2 (M+1).

Workup

  1. temperatureCool the two mixtures in a cold water bath
  2. stirringStir the mixtures at RT for 90 min
  3. additionPour the mixtures
  4. custominto separate separatory funnels along with water (300 mL) and EtOAc (400 mL), shake
  5. custompartition
  6. extractionExtract the aqueous layers with EtOAc (3×300 mL)
  7. washwash the respective organic layers with water (4×250 mL), saturated aqueous NaCl (200 mL)
  8. dry with materialdry over MgSO4
  9. filtrationfilter
  10. concentrationconcentrate under reduced pressure
  11. customPurify the combined materials via silica gel chromatography
  12. washeluting with 70% to 100% EtOAc in hexanes
  13. concentrationCombine and concentrate the purified fractions under reduced pressure
  14. additionDilute the residue with EtOAc (500 mL)
  15. washwash with saturated aqueous NH4Cl (100 mL), saturated aqueous NaHCO3 (100 mL), water (100 mL) and saturated aqueous NaCl (100 mL)
  16. dry with materialDry the organics over MgSO4
  17. filtrationfilter
  18. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-782d6102ce134ed2bca756e9dbebcbc3
Source dataset
uspto-grants-2015_05
Patent number
US09035051B1

Reaction notes

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