1-Bromo-3-cyclopropylbenzene → HCID 53236437, 화합물

HRID 2036030

반응식

HRID 2036030 반응식
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

참가 물질

5

반응물 3

HCID 32826721-Bromo-3-cyclopropylbenzeneHCID 67216150HCID 67216150, 화합물HCID 178418306HCID 178418306, 화합물

생성물 1

HCID 53236437HCID 53236437, 화합물수율 13.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-390ef78ea6584e5d8ab92f003fb466ed
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08575160B2

연결된 노트

불러오는 중…