Diisopropylethylamine → HCID 71576987, compound

HRID 1630341Notes

Reaction equation

HRID 1630341 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([NH:11][C:12]2[N:17]=[C:16]([NH:18][CH3:19])[C:15]([C:20]([F:23])([F:22])[F:21])=[CH:14][N:13]=2)[C:8]([O:24][CH3:25])=[CH:7][C:3]=1[C:4](O)=[O:5].CN(C(O[N:34]1N=N[C:36]2C=CC=[N:40][C:35]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.ONC(=N)C>CN(C=O)C.C(OCC)(=O)C>[F:1][C:2]1[C:3]([C:4]2[O:5][N:40]=[C:35]([CH3:36])[N:34]=2)=[CH:7][C:8]([O:24][CH3:25])=[C:9]([NH:11][C:12]2[N:17]=[C:16]([NH:18][CH3:19])[C:15]([C:20]([F:21])([F:22])[F:23])=[CH:14][N:13]=2)[CH:10]=1

Participants

7

Reactant 4

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 86688209HCID 86688209, compoundHCID 178465666HCID 178465666, compound2×

Product 1

HCID 71576987HCID 71576987, compoundYield 15%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-fluoro-5-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)benzoic acid (0.1 g, 0.28 mmol), HATU (127 mg, 0.33 mmol) and DIPEA (60 uL, 6.33 mmol) in DMF (2 mL) was stirred at room temperature for 5 min. N-Hydroxyacetimidamide (25 mg, 0.33 mmol) was added and the mixture was stirred at room temperature for 30 min followed by 100° C. for 18 h. Additional HATU (127 mg, 0.33 mmol), DIPEA (60 uL, 6.33 mmol) and N-hydroxyacetimidamide (25 mg, 0.33 mmol) were added and the reaction was heated at 100° C. for a further 8 h. The mixture was cooled and diluted with ethyl acetate (10 mL). The organic layer was washed with saturated aqueous NaHCO3 (2×5 mL) and the combined aqueous washes were extracted with further ethyl acetate (2×10 mL). The combined organics were passed through a phase separation cartridge and the solvent removed under reduced pressure. Purification of the residue via silica gel column chromatography (0-100% ethyl acetate/isohexane) afforded N2-(5-fluoro-2-methoxy-4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine as a white solid (16 mg, 15%). LCMS (10 cm_ESCI_Formic_MeCN): [MH+]=399 at 4.51 min. 1H NMR (400 MHz, CDCl3): δ 8.67 (d, J=13, 1H); 8.23 (s, 1H); 8.01 (s, 1H); 7.48 (d, J=6.1, 1H); 5.33 (s, 1H); 4.00 (s, 3H); 3.16 (d, J=4.7, 3H); 2.51-2.44 (m, 3H).

Workup

  1. stirringthe mixture was stirred at room temperature for 30 min
  2. waitfollowed by 100° C. for 18 h
  3. temperaturethe reaction was heated at 100° C. for a further 8 h
  4. temperatureThe mixture was cooled
  5. washThe organic layer was washed with saturated aqueous NaHCO3 (2×5 mL)
  6. extractionthe combined aqueous washes were extracted with further ethyl acetate (2×10 mL)
  7. customThe combined organics were passed through a phase separation cartridge
  8. customthe solvent removed under reduced pressure
  9. customPurification of the residue via silica gel column chromatography (0-100% ethyl acetate/isohexane)

Sources & evidence

ORD record
ord-79308e20cee04a79829f7d5d35fb2f3a
Source dataset
uspto-grants-2014_07
Patent number
US08791130B2

Reaction notes

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