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 1038976ノート

反応式

HRID 1038976 の反応式
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

参加物

9

反応物 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

生成物 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

試薬・触媒・溶媒 4

HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 31374Dimethylacetamide溶媒

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-a3168a038be04db096659fc35dcdfd3b
出典データセット
uspto-grants-2013_10
特許番号
US08552019B2

反応ノート

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