Diisopropylethylamine → N-[(2-chloro-6-ethylphenyl)carbonyl]-4-(1,3,6-trimethyl-2,4-dioxo-5-pyrimidinyl)-L-phenylalanine methyl ester

HRID 844857ノート

反応式

HRID 844857 の反応式
Cl.[CH3:2][O:3][C:4](=[O:25])[C@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:15](=[O:24])[N:16]([CH3:23])[C:17](=[O:22])[N:18]([CH3:21])[C:19]=2[CH3:20])=[CH:10][CH:9]=1)[NH2:6].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl:50][C:51]1[CH:59]=[CH:58][CH:57]=[C:56]([CH2:60][CH3:61])[C:52]=1[C:53](O)=[O:54].C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[CH3:2][O:3][C:4](=[O:25])[C@H:5]([CH2:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[C:15](=[O:24])[N:16]([CH3:23])[C:17](=[O:22])[N:18]([CH3:21])[C:19]=2[CH3:20])=[CH:12][CH:13]=1)[NH:6][C:53]([C:52]1[C:56]([CH2:60][CH3:61])=[CH:57][CH:58]=[CH:59][C:51]=1[Cl:50])=[O:54]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 226137692-Chloro-6-ethylbenzoic acidHCID 693375064-(1,3,6-trimethyl-2,4-dioxo-5-pyrirnidinyl)-L-phenylalanine methyl ester hydrochloride salt

生成物 1

HCID 69335943N-[(2-chloro-6-ethylphenyl)carbonyl]-4-(1,3,6-trimethyl-2,4-dioxo-5-pyrimidinyl)-L-phenylalanine methyl ester収率 70.3%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a suspension of 4-(1,3,6-trimethyl-2,4-dioxo-5-pyrimidinyl)-L-phenylalanine methyl ester hydrochloride salt (0.5 mmol, 184 mg), HBTU (0.7 mmol, 265 mg) and 2-chloro-6-ethylbenzoic acid (0.7 mmol, 129 mg) in DMF (2 mL) was added diisopropylethylamine (1.25 mmol, 0.22 mL) at room temperature. After 5 min, everything went into solution and the clear yellow solution was stirred for 15 h at room temperature. The resulting dark-brown solution was diluted with ethyl acetate (30 mL). The ethyl acetate layer was washed successively with 1N hydrochloric acid (2×30 mL), saturated sodium bicarbonate solution (30 mL), and brine solution (30 mL) and was dried over anhydrous magnesium sulfate. Filtration of the drying agent and concentration of the solvent gave the crude product which was purified by silica gel column chromatography using a Biotage (40m) column to afford 175 mg (70% yield) of N-[(2-chloro-6-ethylphenyl)carbonyl]-4-(1,3,6-trimethyl-2,4-dioxo-5-pyrimidinyl)-L-phenylalanine methyl ester as an amorphous white solid. ES-HRMS m/e calcd for C26H28ClN3O5 (M+Na) 520.1611, found 520.1613.

後処理

  1. washThe ethyl acetate layer was washed successively with 1N hydrochloric acid (2×30 mL), saturated sodium bicarbonate solution (30 mL), and brine solution (30 mL)
  2. dry with materialwas dried over anhydrous magnesium sulfate
  3. filtrationFiltration of the drying agent and concentration of the solvent
  4. customgave the crude product which
  5. customwas purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-c6d316a75bc54cde9ca77a394c4882e0
出典データセット
uspto-grants-2002_04
特許番号
US06380387B1

反応ノート

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