Dimethylformamide → N1-(2-(6-(3-(trifluoromethyl)benzylamino)pyrimidin-4-yl)-4-chlorophenyl)-N3-(2-(2-hydroxyethoxy)ethyl)isophthalamide

HRID 625382Notes

Reaction equation

HRID 625382 reaction equation
[F:1][C:2]([F:26])([F:25])[C:3]1[CH:4]=[C:5]([CH:22]=[CH:23][CH:24]=1)[CH2:6][NH:7][C:8]1[CH:13]=[C:12]([C:14]2[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=2[NH2:21])[N:11]=[CH:10][N:9]=1.CN([C:30]([O:34]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N([CH2:58][CH3:59])C(C)C)(C)C.[C:60]([NH2:71])(=[O:70])[C:61]1[CH:69]=[CH:68][CH:67]=[C:63]([C:64](N)=[O:65])[CH:62]=1.CN(C)[CH:74]=[O:75]>>[F:26][C:2]([F:25])([F:1])[C:3]1[CH:4]=[C:5]([CH:22]=[CH:23][CH:24]=1)[CH2:6][NH:7][C:8]1[N:9]=[CH:10][N:11]=[C:12]([C:14]2[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=2[NH:21][C:64](=[O:65])[C:63]2[CH:67]=[CH:68][CH:69]=[C:61]([C:60]([NH:71][CH2:59][CH2:58][O:34][CH2:30][CH2:74][OH:75])=[O:70])[CH:62]=2)[CH:13]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 74445IsophthalamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 665866436-(2-amino-5-chlorophenyl)-N-(3-(trifluoromethyl)benzyl)pyrimidin-4-amine

Product 1

HCID 66587959N1-(2-(6-(3-(trifluoromethyl)benzylamino)pyrimidin-4-yl)-4-chlorophenyl)-N3-(2-(2-hydroxyethoxy)ethyl)isophthalamideYield 33%

Conditions

Temperature
30 °C

Procedure

Into a 50-mL round bottom flask, was placed a solution of N-(3-(trifluoromethyl)benzyl)-6-(2-amino-5-chlorophenyl)pyrimidin-4-amine (200 mg, 0.53 mmol, 1.00 equiv) in N,N-dimethylformamide (20 mL), HATU (290 mg, 0.76 mmol, 2.00 equiv), N,N-diisopropylethylamine (200 mg, 1.55 mmol, 4.00 equiv), and N1-(2-(6-(3-(trifluoromethyl)benzylamino)pyrimidin-4-yl)-4-chlorophenyl)-N3 hydroxyethoxy)ethyl)isophthalamide (60 mg, 0.10 mmol, 1.50 equiv). The resulting solution was stirred overnight at 30° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting mixture was concentrated under vacuum. The crude product was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 105.9 mg (33%) of a yellow solid. 1H-NMR (300 MHz, DMSO-d6, ppm): δ 8.87 (s, 1H), 8.71 (t, J=4.8 Hz, 9.9 Hz, 1H), 8.49 (s, 1H), 8.07 (t, J=7.5 Hz, 15.3 Hz, 2H), 7.83 (s, 1H), 7.58 (m, 6H), 7.07 (s, 1H), 4.75 (s, 2H), 3.57 (m, 2H), 3.49 (m, 6H). MS (ES, m/z): 614 [M+H]+.

Workup

  1. customInto a 50-mL round bottom flask, was placed
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. customThe crude product was purified by reverse phase HPLC
  4. washeluting with a water/CH3CN gradient
  5. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-2307df78d8ff4179a657cb283b81a313
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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