Dimethylformamide → Trifluoroacetic acid

HRID 2207398Notes

Reaction equation

HRID 2207398 reaction equation
C(NC(C)C)(C)C.[NH2:8][CH2:9][CH:10]([OH:13])[CH2:11][OH:12].F[P-](F)(F)(F)(F)F.N1([O:30][P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[CH3:41][C:42]1[CH:43]=[C:44]([C:59]2[CH:60]=[C:61]([C:65](O)=[O:66])[CH:62]=[N:63][CH:64]=2)[CH:45]=[C:46]([NH:48][C:49]2[N:54]=[C:53]([C:55]([F:58])([F:57])[F:56])[CH:52]=[CH:51][N:50]=2)[CH:47]=1.CN([CH:71]=[O:72])C>O>[OH:13][CH:10]([CH2:11][OH:12])[CH2:9][NH:8][C:65]([C:61]1[CH:62]=[N:63][CH:64]=[C:59]([C:44]2[CH:45]=[C:46]([NH:48][C:49]3[N:54]=[C:53]([C:55]([F:58])([F:56])[F:57])[CH:52]=[CH:51][N:50]=3)[CH:47]=[C:42]([CH3:41])[CH:43]=2)[CH:60]=1)=[O:66].[C:71]([OH:72])([C:55]([F:58])([F:57])[F:56])=[O:30]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 735613-Amino-1,2-propanediolHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 131735906HCID 131735906, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 118092866HCID 118092866, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

N,N-diisopropylamine (99 μL, 0.57 mmol), 3-aminopropane-1,2-diol (35 mg, 0.38 mmol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (130 mg, 0.29 mmol) were added to a solution of 5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridine-3-carboxylic acid (71 mg, 0.19 mmol) in DMF (0.6 mL) and the reaction mixture was stirred for 20 hours at room temperature. The reaction mixture was diluted with water and extracted with dichloromethane, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by reverse phase HPLC to afford N-(2,3-dihydroxypropyl)-5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridine-3-carboxamide as a TFA salt. MS ESI calc'd for C21H21F3N5O3 [M+H]+ 448. found 448. 1H NMR (500 MHz, DMSO-d6) δ 10.29 (s, 1H), 8.97 (s, 1H), 8.93 (s, 1H), 8.89-8.79 (m, 1H), 8.78-8.68 (m, 1H), 8.46-8.34 (m, 1H), 8.04-7.93 (m, 1H), 7.60 (s, 1H), 7.32-7.22 (m, 2H), 3.69-3.63 (m, 1H), 3.48-3.39 (m, 2H), 3.25-3.17 (m, 2H), 2.66-2.58 (m, 1H), 2.38 (s, 3H), 2.37-2.32 (m, 1H).

Workup

  1. extractionextracted with dichloromethane
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-3b9efdc8ebad44759669ca3711fc8f79
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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