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

HRID 2036030

Reaction equation

HRID 2036030 reaction equation
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

Participants

5

Reactant 3

HCID 32826721-Bromo-3-cyclopropylbenzeneHCID 67216150HCID 67216150, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 53236437HCID 53236437, compoundYield 13.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-390ef78ea6584e5d8ab92f003fb466ed
Source dataset
uspto-grants-2013_11
Patent number
US08575160B2

Linked notes

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