Diisopropylethylamine → HCID 178475042、化合物

HRID 2246604ノート

反応式

HRID 2246604 の反応式
[NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([C@H:7]2[CH2:12][CH2:11][C@@H:10]([NH:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:9][C@H:8]2[NH:18][C:19](=[O:21])[CH3:20])[C:3]1=[O:22].O([C:30]1[C:39]2[C:34](=[CH:35][CH:36]=[C:37]([C:40]([F:43])([F:42])[F:41])[CH:38]=2)[N+:33]([O-:44])=[CH:32][N:31]=1)C1C=CC=CC=1.C(N(CC)C(C)C)(C)C>CC(O)C>[C:19]([NH:18][C@@H:8]1[CH2:9][C@H:10]([NH:13][C:14]([CH3:17])([CH3:15])[CH3:16])[CH2:11][CH2:12][C@@H:7]1[N:4]1[CH2:5][CH2:6][C@H:2]([NH:1][C:30]2[C:39]3[C:34](=[CH:35][CH:36]=[C:37]([C:40]([F:43])([F:41])[F:42])[CH:38]=3)[N+:33]([O-:44])=[CH:32][N:31]=2)[C:3]1=[O:22])(=[O:21])[CH3:20]

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 67180344N-((1R,2S,5R)-2-((S)-3-amino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexyl)acetamideHCID 685663764-Phenoxy-6-(trifluoromethyl)quinazoline 1-oxide

生成物 1

HCID 178475042HCID 178475042、化合物収率 120%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

反応条件

温度
120 °C

実験手順

To a solution of N-((1R,2S,5R)-2-((S)-3-amino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexyl)acetamide (50 mg, 0.161 mmol, prepared as described above) and 4-phenoxy-6-(trifluoromethyl)quinazoline 1-oxide (99 mg, 0.161 mmol; see Example 5, Alternative Preparation, Step 2) in i-PrOH (2 ml) was added N,N-diisopropylethylamine (0.056 ml, 0.322 mmol). The vessel was sealed under argon atmosphere and heated in a microwave for 1 hr at 120° C. LC/MS found: (M+H)+=523.3 as the major product peak. The reaction was repeated on the same scale in a separate vessel. The two reactions were combined and evaporated to give an oily residue, which was purified by automated flash chromatography (40 g silica gel) with elution by 8:92 (10% cNH4OH in MeOH). The fractions containing the desired product were pooled and concentrated in vacuo. The residue was crystallized from CH2Cl2 and hexane. The two crops were combined and dried under vacuum to afford 4-((S)-1-((1S,2R,4R)-2-acetamido-4-(tert-butylamino)cyclohexyl)-2-oxopyrrolidin-3-ylamino)-6-(trifluoromethyl)quinazoline 1-oxide (101 mg). Analysis by 1H-NMR showed that this material contained ˜0.6 molar equivalents of CH2Cl2. LC/MS found: [M+H]+=523.30. 1H-NMR (400 MHz, CD3OD), δ ppm: 9.00 (s, 1H), 8.80 (s, 1H), 8.61 (d, J=9.0 Hz, 1H), 8.32 (dd, J=9.0, 1.6 Hz, 1H), 5.28 (t, J=8.3 Hz, 1H), 4.57 (brs, 1H), 4.02 (brd, 1H), 3.65-3.51 (m, 2H), 3.24 (brs, 1H), 2.59-2.51 (m, 1H), 2.34-2.20 (m, 1H), 2.04 (s, 3H), 2.04 (m, 1H), 1.89 (brs, 3H), 1.74 (brs, 2H), 1.20 (s, 9H).

後処理

  1. customThe vessel was sealed under argon atmosphere
  2. customThe reaction was repeated on the same scale in a separate vessel
  3. customevaporated
  4. customto give an oily residue, which
  5. customwas purified by automated flash chromatography (40 g silica gel) with elution by 8:92 (10% cNH4OH in MeOH)
  6. additionThe fractions containing the desired product
  7. concentrationconcentrated in vacuo
  8. customThe residue was crystallized from CH2Cl2 and hexane
  9. customdried under vacuum

出典と根拠

ORDレコード
ord-fd5b6645324a49d1ad192571fd80b702
出典データセット
uspto-grants-2010_03
特許番号
US07687508B2

反応ノート

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