1-Bromo-3-cyclopropylbenzene → HCID 53236437、化合物

HRID 2036030

反応式

HRID 2036030 の反応式
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH:8]2[CH2:10][CH2:9]2)[CH:3]=1.[Li]C(C)(C)C.[F:16][C:17]1[CH:18]=[C:19]([CH:22]=[CH:23][C:24]=1[C@@H:25]1[N:29]2[CH:30]=[N:31][CH:32]=[C:28]2[C:27](=[O:33])[CH2:26]1)[C:20]#[N:21]>C1COCC1>[CH:8]1([C:4]2[CH:3]=[C:2]([C@:27]3([OH:33])[C:28]4[N:29]([CH:30]=[N:31][CH:32]=4)[C@@H:25]([C:24]4[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][C:17]=4[F:16])[CH2:26]3)[CH:7]=[CH:6][CH:5]=2)[CH2:10][CH2:9]1

参加物

5

反応物 3

HCID 32826721-Bromo-3-cyclopropylbenzeneHCID 67216150HCID 67216150、化合物HCID 178418306HCID 178418306、化合物

生成物 1

HCID 53236437HCID 53236437、化合物収率 13.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

To a solution of 1-bromo-3-cyclopropyl-benzene (0.018 ml, 0.124 mmol) in THF (0.2 ml) cooled to −78° C. was added a solution of 1.6 M t-BuLi (0.155 ml, 0.249 mmol). The crude was stirred at −78° C. for 2 hrs. To this solution was add a solution of 3-fluoro-4-((R)-7-oxo-6,7-dihydro-5H pyrrolo[1,2-c]imidazol-5-yl)-benzonitrile (20 mg, 0.083 mmol) in THF (0.2 ml). The crude was stirred at −78° C. for 1 hr, then at 0° C. for 1 hr and room temperature for 1 hr. This reaction was quenched with water and extract the aq. with CH2Cl2. The organic layer was dried over Na2SO4, filtered, and concentrated. The crude was purified via preparation plate using 10% (2M NH3 in MeOH)/CH2Cl2. The entitled product (4 mg) was isolated as the major diastereomer. MS 360.1 (M+H); LCMS condition B, retention time 1.16 min. 1H NMR (400 MHz, CDCl3) δ ppm 0.52-0.65 (m, 2H), 0.85-0.95 (m, 2H), 1.74-1.91 (m, 1H), 2.57 (br. s., 1H), 2.92 (d, 1H), 3.30 (dd, 1H), 5.73 (d, 1H), 6.91 (s, 1H), 6.96 (ddd, 1H), 7.12 (t, 1H), 7.16-7.28 (m, 3H), 7.29-7.41 (m, 2H), 7.42-7.53 (m, 1H).

後処理

  1. stirringThe crude was stirred at −78° C. for 1 hr
  2. waitat 0° C. for 1 hr
  3. waitroom temperature for 1 hr
  4. customThis reaction was quenched with water
  5. extractionextract the aq. with CH2Cl2
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude was purified via preparation plate

出典と根拠

ORDレコード
ord-390ef78ea6584e5d8ab92f003fb466ed
出典データセット
uspto-grants-2013_11
特許番号
US08575160B2

関連ノート

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