Diisopropylethylamine → 1-(3,4-difluorobenzyl)-6-oxo-N-{(1R)-2-[(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)oxy]-1-phenylethyl}-1,6-dihydropyrimidine-5-carboxamide

HRID 1038976Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1038976
Cl.[NH2:2][C@H:3]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:9]2[NH:10][C:11](=[O:13])[NH:12][C:8]=2[CH:7]=1.[F:22][C:23]1[CH:24]=[C:25]([CH:37]=[CH:38][C:39]=1[F:40])[CH2:26][N:27]1[C:32](=[O:33])[C:31]([C:34](O)=[O:35])=[CH:30][N:29]=[CH:28]1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CC(N(C)C)=O.O.C(#N)C.CS(C)=O>[F:22][C:23]1[CH:24]=[C:25]([CH:37]=[CH:38][C:39]=1[F:40])[CH2:26][N:27]1[C:32](=[O:33])[C:31]([C:34]([NH:2][C@H:3]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:4][O:5][C:6]2[CH:15]=[CH:14][C:9]3[NH:10][C:11](=[O:13])[NH:12][C:8]=3[CH:7]=2)=[O:35])=[CH:30][N:29]=[CH:28]1

Komponenten

9

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 584430401-(3,4-Difluorobenzyl)-6-oxo-1,6-dihydropyrimidine-5-carboxylic acidHCID 673985985-[(2R)-2-amino-2-phenylethoxy]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

Produkt 1

HCID 462094061-(3,4-difluorobenzyl)-6-oxo-N-{(1R)-2-[(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)oxy]-1-phenylethyl}-1,6-dihydropyrimidine-5-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

To a solution of 5-[(2R)-2-amino-2-phenylethoxy]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (38 mg, 0.124 mmol), 1-(3,4-difluorobenzyl)-6-oxo-1,6-dihydropyrimidine-5-carboxylic acid (33.1 mg, 0.124 mmol) and N,N-diisopropylethylamine (65.1 μl, 0.373 mmol) in DMA (710 μl), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (54.3 mg, 0.143 mmol) was added. After stirring for 90 minutes at room temperature, the reaction mixture was diluted with water, acetonitrile, and DMSO. This solution was purified by preparative HPLC Reverse phase (C-18), eluting with Acetonitrile/Water+0.05% TFA, to afford 1-(3,4-difluorobenzyl)-6-oxo-N-{(1R)-2-[(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)oxy]-1-phenylethyl}-1,6-dihydropyrimidine-5-carboxamide as a white solid after neutralization, extraction, and drying of HPLC fractions. 1H NMR (500 MHz, C2D6SO) δ 10.51 (s, 1H), 10.38 (s, 1H), 9.73 (d, 1H), 8.95 (s, 1H), 8.67 (s, 1H), 7.52 (m, 1H), 7.41 (m, 3H), 7.34 (t, 2H), 7.25 (m, 2H), 6.74 (d, 1H), 6.49 (d, 2H), 5.36 (m, 1H), 5.19 (t, 2H), 4.26 (m, 1H), 4.19 (m, 1H). LRMS (ESI) calc'd for (C27H22F2N5O4) [M+H]+, 518.2; found 518.1.

Aufarbeitung

  1. customThis solution was purified by preparative HPLC Reverse phase (C-18)
  2. washeluting with Acetonitrile/Water+0.05% TFA

Quellen und Nachweise

ORD-Eintrag
ord-a3168a038be04db096659fc35dcdfd3b
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08552019B2

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