Diisopropylethylamine → HCID 178456065、化合物

HRID 1625138

反応式

HRID 1625138 の反応式
[NH2:1][C@H:2]([C:5]1[N:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:13](=[O:21])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][C:11]=2[F:22])[N:6]=1)[CH2:3][CH3:4].Br[C:24]1[N:32]=[CH:31][N:30]=[C:29]2[C:25]=1[NH:26][CH:27]=[N:28]2.CCN(C(C)C)C(C)C>C(O)(C)(C)C.CCO>[F:22][C:11]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:12]=1[C:13](=[O:21])[N:14]([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[C:5]([C@@H:2]([NH:1][C:24]1[N:32]=[CH:31][N:30]=[C:29]3[C:25]=1[N:26]=[CH:27][NH:28]3)[CH2:3][CH3:4])=[N:6]2

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 5287830Purine, 6-bromo-HCID 598410522-[(1S)-1-Aminopropyl]-5-fluoro-3-phenyl-4(3H)-quinazolinone

生成物 1

HCID 178456065HCID 178456065、化合物

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 6386tert-Butanol溶媒

反応条件

温度
80 °C

実験手順

A suspension of compound 111 (65.6 mmol, 1 eq), 6-bromopurine (14.6 g, 73.4 mmol, 1.1 eq), and DIEA (24.3 mL, 140 mmol, 2 eq) in tert-butanol (40 mL) was stirred for 24 h at 80° C. The reaction mixture was concentrated in vacuo and treated with water to yield a solid crude product that was collected by vacuum filtration, washed with water, and air dried. Half of the obtained solid crude product was dissolved in MeOH (600 mL), concentrated onto silica gel (300 mL dry), and purified by flash chromatography (7.5×36 cm, eluted with 10 L of 4% MeOH/CH2Cl2) to yield a solid product. The solid product was then dissolved in EtOH (250 mL) and concentrated in vacuo to compound 107 as a light yellow solid (7.2 g, 50%). 1H NMR (300 MHz, 80° C., DMSO-d6) δ 12.66 (broad s, 1H), 8.11 (s, 1H), 8.02 (broad s, 1H), 7.81-7.73 (m, 1H), 7.60-7.42 (m, 6H), 7.25-7.15 (m, 2H), 4.97 (broad s, 1H), 2.02-1.73 (m, 2H), 0.79 (t, J=7.3 Hz, 3H). ESI-MS m/z 416.2 (MH+). C, H, N elemental analysis (C22H18N7OF.EtOH.0.4 H2O). Chiral purity 99.8:0.2 (S:R) using chiral HPLC (4.6×250 mm Chiralpak ODH column, 20° C., 85:15 hexanes:EtOH, 1 mL/min, sample loaded at a concentration of 1 mg/mL in EtOH). The reaction described above and compound 107 are shown below.

後処理

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additiontreated with water
  3. customto yield a solid crude product that
  4. filtrationwas collected by vacuum filtration
  5. washwashed with water, and air
  6. customdried
  7. dissolutionHalf of the obtained solid crude product was dissolved in MeOH (600 mL)
  8. concentrationconcentrated onto silica gel (300 mL dry)
  9. custompurified by flash chromatography (7.5×36 cm, eluted with 10 L of 4% MeOH/CH2Cl2)
  10. customto yield a solid product
  11. concentrationconcentrated in vacuo to compound 107 as a light yellow solid (7.2 g, 50%)
  12. custom4.6×250 mm Chiralpak ODH column, 20° C., 85:15 hexanes

出典と根拠

ORDレコード
ord-73cfbb3c4f5542579605086ce5e63665
出典データセット
uspto-grants-2014_07
特許番号
US08779131B2

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