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 1038976노트

반응식

HRID 1038976 반응식
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

참가 물질

9

반응물 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

생성물 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

시약·촉매·용매 4

HCID 679Dimethyl Sulfoxide용매HCID 962Water용매HCID 6342Acetonitrile용매HCID 31374Dimethylacetamide용매

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-a3168a038be04db096659fc35dcdfd3b
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08552019B2

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