Diisopropylethylamine → HCID 178475041、化合物

HRID 2246583ノート

反応式

HRID 2246583 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]([N:13]([CH:15]([CH3:17])[CH3:16])[CH3:14])[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]([N:13]([CH:15]([CH3:17])[CH3:16])[CH3:14])[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 44185161N-((1R,2S,5R)-2-((S)-3-amino-2-oxopyrrolidin-1-yl)-5-(isopropyl(methyl)amino)cyclohexyl)acetamideHCID 685663764-Phenoxy-6-(trifluoromethyl)quinazoline 1-oxide

生成物 1

HCID 178475041HCID 178475041、化合物収率 110.5%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

反応条件

温度
120 °C

実験手順

Example 5, Alternative Preparation, Step 3: To a solution of N-((1R,2S,5R)-2-((S)-3-amino-2-oxopyrrolidin-1-yl)-5-(isopropyl(methyl)amino)cyclohexyl)acetamide (50 mg, 0.161 mmol; see Example 1, Step 10) and 4-phenoxy-6-(trifluoromethyl)quinazoline 1-oxide (99 mg, 0.161 mmol) in i-PrOH (2 ml) was added N,N-diisopropylethylamine (0.056 ml, 0.322 mmol). The vessel was sealed under argon and heated in a microwave for 1 hr at 120° C. LC/MS found: (M+H)+=523.3 as the major product peak. The mixture was concentrated and purified by automated flash chromatography (40 g silica gel, eluting with 8:92 10% cNH4OH/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 the title compound, 4-((S)-1-((1S,2R,4R)-2-acetamido-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-ylamino)-6-(trifluoromethyl)quinazoline 1-oxide (93 mg). Analysis by 1H-NMR showed that this material contained ˜0.75 molar equivalents of CH2Cl2. 1H-NMR (400 MHz, d4-MeOH): δ 8.99 (s, 1H), 8.81 (s, 1H), 8.62 (d, J=8.9 Hz, 1H), 8.32 (dd, J=9.0, 1.5 Hz, 1H), 5.28 (t, J=8.4 Hz, 1H), 4.59 (br s, 1H), 4.05 (m, 1H), 3.55-3.65 (m, 2H), 3.43 (m, 1H), 2.75 (br s, 1H), 2.55 (m, 1H), 2.27 (s, 3H), 2.1-2.3 (m, 3H), 2.02 (s, 3H), 2.0 (m, 1H), 1.65-1.7 (m, 3H), 1.12 (d, J=6.0 Hz, 3H), 1.06 (d, J=6.0 Hz, 3H). LC/MS found: [M+H]+=523.33.

後処理

  1. customExample 5, Alternative Preparation, Step 3
  2. customThe vessel was sealed under argon
  3. concentrationThe mixture was concentrated
  4. custompurified by automated flash chromatography (40 g silica gel, eluting with 8:92 10% cNH4OH/MeOH)
  5. additionThe fractions containing the desired product
  6. concentrationconcentrated in vacuo
  7. customThe residue was crystallized from CH2Cl2 and hexane
  8. customdried under vacuum

出典と根拠

ORDレコード
ord-6f990ef72e5e40c383fd1deaa08c2bc7
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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