4-Methylmorpholine → {2-Methyl-1-[2-(5-{6-[4-(2-{1-[2-phenyl-2-(2-tetrahydro-pyran-4-yl-acetylamino)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carbonyl]-propyl}-carbamic acid methyl ester

HRID 1751505ノート

反応式

HRID 1751505 の反応式
[CH3:1][O:2][C:3](=[O:57])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:30]=[CH:29][C:28]3[C:23](=[CH:24][CH:25]=[C:26]([C:31]4[CH:36]=[CH:35][C:34]([C:37]5[NH:38][C:39]([CH:42]6[CH2:46][CH2:45][CH2:44][N:43]6[C:47](=[O:56])[CH:48]([NH2:55])[C:49]6[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=6)=[N:40][CH:41]=5)=[CH:33][CH:32]=4)[CH:27]=3)[CH:22]=2)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].[O:58]1[CH2:63][CH2:62][CH:61]([CH2:64][C:65](O)=[O:66])[CH2:60][CH2:59]1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:1][O:2][C:3](=[O:57])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:30]=[CH:29][C:28]3[C:23](=[CH:24][CH:25]=[C:26]([C:31]4[CH:32]=[CH:33][C:34]([C:37]5[NH:38][C:39]([CH:42]6[CH2:46][CH2:45][CH2:44][N:43]6[C:47](=[O:56])[CH:48]([C:49]6[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=6)[NH:55][C:65](=[O:66])[CH2:64][CH:61]6[CH2:62][CH2:63][O:58][CH2:59][CH2:60]6)=[N:40][CH:41]=5)=[CH:35][CH:36]=4)[CH:27]=3)[CH:22]=2)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 2773575Tetrahydropyran-4-ylacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 69675184[1-(2-{5-[6-(4-{2-[1-(2-Amino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester

生成物 1

HCID 69675095{2-Methyl-1-[2-(5-{6-[4-(2-{1-[2-phenyl-2-(2-tetrahydro-pyran-4-yl-acetylamino)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carbonyl]-propyl}-carbamic acid methyl ester収率 71.7%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

[1-(2-{5-[6-(4-{2-[1-(2-Amino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester (0.085 g, 0.097 mmol), (Tetrahydro-pyran-4-yl)-acetic acid (0.017 g, 0.117 mmol), and N-methylmorpholine (0.032 mL, 0.292 mmol) were suspended in DMF (0.972 mL) at room temperature. Solid HATU (0.055 g, 0.146 mmol) was added and the suspension was allowed to stir at room temperature overnight. Upon completion, the reaction was quenched with a small amount of formic acid and purified by reverse phase HPLC (10-45% acetonitrile:water; 0.1% formic acid modifier), and lyophilized giving {2-Methyl-1-[2-(5-{6-[4-(2-{1-[2-phenyl-2-(2-tetrahydro-pyran-4-yl-acetylamino)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carbonyl]-propyl}-carbamic acid methyl ester (0.062 g, 62%) as a white solid. LCMS-ESI+: calc'd for C52H58N8O6: 890.45 (M+); Found: 892.4 (M+H+).

後処理

  1. customUpon completion, the reaction was quenched with a small amount of formic acid
  2. custompurified by reverse phase HPLC (10-45% acetonitrile:water; 0.1% formic acid modifier)

出典と根拠

ORDレコード
ord-18b37b8cbca04c739110c024bf2e70ee
出典データセット
uspto-grants-2015_10
特許番号
US09156823B2

反応ノート

読み込み中…