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Oxalyl chloride → 2-{1-[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-cyclopropyl}-N-(4-methoxy-benzyl)-acetamide

HRID 2194769
ノート
印刷プレビュー

反応式

HRID 2194769 の反応式
[C:1]([C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([CH3:30])[CH:29]=1)[C:6]([C:8]1[N:13]([CH2:14][C:15]2([CH2:18][C:19](O)=[O:20])[CH2:17][CH2:16]2)[C:12](=[O:22])[NH:11][C:10](=[O:23])[C:9]=1[CH:24]([CH3:26])[CH3:25])=[O:7])#[N:2].C(Cl)(=O)C(Cl)=O.[CH3:37][O:38][C:39]1[CH:46]=[CH:45][C:42]([CH2:43][NH2:44])=[CH:41][CH:40]=1>C1COCC1.CN(C=O)C>[C:1]([C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([CH3:30])[CH:29]=1)[C:6]([C:8]1[N:13]([CH2:14][C:15]2([CH2:18][C:19]([NH:44][CH2:43][C:42]3[CH:45]=[CH:46][C:39]([O:38][CH3:37])=[CH:40][CH:41]=3)=[O:20])[CH2:16][CH2:17]2)[C:12](=[O:22])[NH:11][C:10](=[O:23])[C:9]=1[CH:24]([CH3:26])[CH3:25])=[O:7])#[N:2]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 65578Oxalyl chlorideHCID 754524-MethoxybenzylamineHCID 25215194{1-[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-cyclopropyl}-acetic acid

生成物 1

HCID 582034682-{1-[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-cyclopropyl}-N-(4-methoxy-benzyl)-acetamide収率 83.4%

試薬・触媒・溶媒 2

HCID 6228
Dimethylformamide
触媒
HCID 8028Tetrahydrofuran溶媒

実験手順

To a stirred solution of {1-[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-cyclopropyl}-acetic acid (90 mg, 0.22 mmol) in THF (5 mL) cooled in an ice bath, were added oxalyl chloride (38 μL, 0.44 mmol) and one drop of DMF. After stirring for 1 hr., the mixture was evaporated in vacuo. The residue was dissolved in THF (8 mL) and p-methoxy benzylamine (261 μL, 2 mmol) was added. After stirring for 1 hr., the mixture was evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, ethyl acetate:hexane (2:1): Rf=0.25 fraction was collected) to give 97 mg (83%) of 2-{1-[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-cyclopropyl}-N-(4-methoxy-benzyl)-acetamide (84) as a white solid. 1H-NMR (200 MHz, CDCl3) δ 0.40-0.46 (4H, m), 1.12 (3H, d, J=6.6 Hz), 1.23 (3H, d, J=6.6 Hz), 2.00 (1H, d, J=15.4 Hz), 2.25 (1H, m), 2.48-2.55 (4H, m), 3.45 (1H., d, J=15.4 Hz), 3.80 (3H, s), 3.90 (1H, d, J=15.4 Hz), 4.34-4.39 (2H, m), 6.69 (1H, m), 6.83-6.90 (2H, m), 7.22-7.30 (2H, m), 7.81 (1H, s), 8.01 (1H, s), 8.07 (1H, s), 9.81 (1H, s).

後処理

  1. custom, the mixture was evaporated in vacuo
  2. dissolutionThe residue was dissolved in THF (8 mL)
  3. stirringAfter stirring for 1 hr
  4. custom, the mixture was evaporated in vacuo
  5. customthe residue was purified by silica gel column chromatography (eluent, ethyl acetate:hexane (2:1): Rf=0.25 fraction was collected)

出典と根拠

ORDレコード
ord-9cc80b76d8de48018ab2116a4b0226ca
出典データセット
uspto-grants-2012_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08334295B2

反応ノート

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