Trifluoroacetic acid → HCID 69297571, compound

HRID 1930433Notes

Reaction equation

HRID 1930433 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[C:18]([C:20]3[C:32](=[O:33])[N:31]([CH3:34])[C:23]4[N:24]=[C:25](S(C)=O)[N:26]=[CH:27][C:22]=4[CH:21]=3)[CH:17]=[CH:16][C:15]=2[F:35])=[O:12])[O:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:36][N:37]([CH2:39][CH2:40][NH2:41])[CH3:38].C(O)(C(F)(F)F)=O>CN(C=O)C.[Cl-].[Na+].O>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[C:18]([C:20]3[C:32](=[O:33])[N:31]([CH3:34])[C:23]4[N:24]=[C:25]([NH:41][CH2:40][CH2:39][N:37]([CH3:38])[CH3:36])[N:26]=[CH:27][C:22]=4[CH:21]=3)[CH:17]=[CH:16][C:15]=2[F:35])=[O:12])[O:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 66053N,N-DimethylethylenediamineHCID 69040323HCID 69040323, compound

Product 1

HCID 69297571HCID 69297571, compoundYield 23.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a stirring solution of 1-(3-t-butylisoxazol-5-yl)-3-(2-fluoro-5-(8-methyl-2-(methylsulfinyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl)phenyl)urea from Example 43 (0.125 g, 0.251 mmol, 1.00 eq) in DMF (2.50 ml) at 0° C. was added unsym-dimethylethylenediamine (0.138 ml, 1.25 mmol, 5.00 eq). After 1 h, the completed reaction was diluted with brine (5 ml) and left to stir overnight. The solids were collected by filtration, rinsed well with H2O and dried on the filter to afford crude desired product (76 mg) as a pale pink solid. The crude product was purified by reverse phase chromatography (5-40% MeCN (w/0.1% TFA)/H2O (w/0.1% TFA)) to afford 1-(3-t-butylisoxazol-5-yl)-3-(5-(2-(2-(dimethylamino)ethylamino)-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl)-2-fluorophenyl)urea (37.3 mg, 0.059 mmol) as the TFA salt following lyophilization. The TFA salt thus obtained was treated with MP-Carbonate resin and certified 0.1N HCl (1.0 eq), frozen and lyophilized to afford the HCl salt. 1H NMR (400 MHz, DMSO-d6): δ 10.44 (s, 1H), 9.56 (brs, 1H), 8.85 (brs, 1H), 8.76 (brs, 1H), 8.41 (dd, J=2.0 and 7.6 Hz, 1H), 8.01 (brs, 1H), 7.95 (s, 1H), 7.37-7.28 (m, 2H), 6.05 (s, 1H), 3.73 (m, 2H), 3.58 (brs, 3H), 3.41 (brs, 2H), 2.85 (brs, 6H), 1.24 (s, 9H); MS (ESI) m/z: 523.2 (M+H+).

Workup

  1. customthe completed reaction
  2. waitleft
  3. filtrationThe solids were collected by filtration
  4. washrinsed well with H2O
  5. customdried on the
  6. filtrationfilter
  7. customto afford crude desired product (76 mg) as a pale pink solid
  8. customThe crude product was purified by reverse phase chromatography (5-40% MeCN (w/0.1% TFA)/H2O (w/0.1% TFA))

Sources & evidence

ORD record
ord-1bcb80d9cd4c46ee98d1af9788d53b8a
Source dataset
uspto-grants-2012_05
Patent number
US08188113B2

Reaction notes

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