L-Azetidine-2-carboxylic acid → HCID 72705769, compound

HRID 2207366Notes

Reaction equation

HRID 2207366 reaction equation
F[C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][N:17]=3)[CH:11]=[C:12]([CH3:14])[CH:13]=2)=[CH:4][CH:3]=1.[NH:26]1[CH2:29][CH2:28][C@H:27]1[C:30]([OH:32])=[O:31].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>>[CH3:14][C:12]1[CH:13]=[C:8]([C:5]2[CH:4]=[CH:3][C:2]([N:26]3[CH2:29][CH2:28][C@H:27]3[C:30]([OH:32])=[O:31])=[N:7][CH:6]=2)[CH:9]=[C:10]([NH:15][C:16]2[N:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][N:17]=2)[CH:11]=1

Participants

4

Reactant 3

HCID 16486L-Azetidine-2-carboxylic acidHCID 62657Potassium Phosphate, TribasicHCID 131735891HCID 131735891, compound

Product 1

HCID 72705769HCID 72705769, compound

Conditions

Temperature
130 °C

Procedure

N-[3-(6-Fluoropyridin-3-yl)-5-methylphenyl]-4-(trifluoromethyl)pyrimidin-2-amine (15.0 g, 43.1 mmol), (2S)-azetidine-2-carboxylic acid (5.23 g, 51.7 mmol) and tripotassium phosphate (18.3 g, 86.0 mmol) are flushed and purged with N2(g) (3×) and DMSO (107 mL) was added. The reaction mixture was heated to 130° C. for 6 hours, then cooled to room temperature and was stirred overnight. The CELITE was added to the reaction mixture, filtered and precipitated by addition of acetonitrile (ca. 300 mL). The crude product was collected by filtration and purified by reverse phase chromatography to yield (2S)-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]azetidine-2-carboxylic acid. MS ESI calc'd for C21H19F3N5O2 [M+H]+ 430. found 430. 1H NMR (600 MHz, CDCl3) δ 8.64 (d, J=4.7 Hz, 1H), 8.29 (s, 1H), 7.85 (d, J=8.5 Hz, 1H), 7.77 (s, 1H), 7.43 (s, 1H), 7.27 (s, 1H), 7.06-6.94 (m, 2H), 6.50 (d, J=8.6 Hz, 1H), 4.88 (t, J=8.1 Hz, 1H), 3.90 (dd, J=8.2 Hz, 16.3 Hz, 2H), 3.03-2.88 (m, 1H), 2.49 (d, J=8.3 Hz, 1H), 2.40 (s, 3H).

Workup

  1. custompurged with N2(g) (3×) and DMSO (107 mL)
  2. additionwas added
  3. temperaturecooled to room temperature
  4. additionThe CELITE was added to the reaction mixture
  5. filtrationfiltered
  6. customprecipitated by addition of acetonitrile (ca. 300 mL)
  7. filtrationThe crude product was collected by filtration
  8. custompurified by reverse phase chromatography

Sources & evidence

ORD record
ord-8ae560af58af4b90afe013a66275e1d4
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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