Diisopropylamine → HCID 86681334, compound

HRID 403340

Reaction equation

HRID 403340 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[Br:13][C:14]1[CH:19]=[N:18][CH:17]=[CH:16][N:15]=1.[F:20][C:21]1[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=1[C@H:28]([CH2:37][CH2:38][CH:39]=[CH2:40])/[CH:29]=[N:30]/[S@@:31]([C:33]([CH3:36])([CH3:35])[CH3:34])=[O:32]>O1CCCC1.C(OCC)(=O)C.CCCCCC>[Br:13][C:14]1[C:19]([C@@H:29]([NH:30][S@@:31]([C:33]([CH3:36])([CH3:35])[CH3:34])=[O:32])[C@H:28]([C:22]2[CH:23]=[CH:24][CH:25]=[C:26]([F:27])[C:21]=2[F:20])[CH2:37][CH2:38][CH:39]=[CH2:40])=[N:18][CH:17]=[CH:16][N:15]=1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 6428002-BromopyrazineHCID 89158770HCID 89158770, compoundHCID 178418339Butyllithium

Product 1

HCID 86681334HCID 86681334, compoundYield 62.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
-30 °C

Procedure

In an oven-dried 250 mL round-bottomed flask was dissolved diisopropylamine (1.7 mL, 12 mmol) in tetrahydrofuran (40 mL) to give a colorless solution under nitrogen. After cooling to −30° C., n-BuLi (4.3 mL, 11 mmol) was added, and the mixture was briefly warmed up to rt for 3 min. After cooling down to −78° C., 2-bromopyrazine (0.98 mL, 10.7 mmol) was added dropwise via syringe. The resulting yellow solution was stirred at −78° C. for 5 min. (R,E)-N—((S)-2-(2,3-difluorophenyl)hex-5-enylidene)-2-methylpropane-2-sulfinamide (2.089 g, 6.67 mmol) in 4 mL anhydrous tetrahydrofuran (plus 3 mL rinse) was added via canuula, and the mixture was stirred for 2 h at −75° C. The reaction was quenched with saturated sodium bicarbonate solution and diluted with ethyl acetate. The layers were separated. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried, and concentrated to give a tan oil. Flash column chromatography up to 80% ethyl acetate/hexane afforded the desired product (1.964 g, 62%) as a dense tan oil: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.33 (d, J=2.26 Hz, 1H) 8.26 (d, J=2.26 Hz, 1H) 6.99-7.22 (m, 3H) 5.74 (d, J=6.53 Hz, 1H) 5.18 (dd, J=9.29, 5.27 Hz, 1H) 4.85-4.99 (m, 2H) 4.30 (d, J=9.54 Hz, 1H) 3.66-3.77 (m, 1H) 2.17 (br. s., 1H) 1.80-2.04 (m, 3H) 1.05 (s, 9H); 19F NMR (376 MHz, CHLOROFORM-d) δ ppm −138.41 (d, J=15.61 Hz, 1F) −144.20-−143.20 (m, 1F); 13C NMR (101 MHz, CHLOROFORM-d) δ ppm 155.19 (s, 1C) 151.32-149.72 (dd, J=13.87 and 249.47 Hz, 1C) 150.24-147.67 (dd, J=12.72 and 246.95 Hz, 1C) 142.89 (s, 1C) 141.44 (br. s., 1C) 140.47 (s, 1C) 136.93 (d, J=10.02 Hz, 1C) 127.54 (d, J=10.79 Hz, 1C) 124.12-124.96 (m, 1C) 123.41-123.97 (m, 1C) 115.23-115.83 (m, 1C) 115.09 (s, 1C) 59.93-60.56 (m, 1C) 56.10-56.69 (m, 1C) 40.72-41.81 (m, 1C) 30.81 (s, 1C) 30.34 (br. s., 1C) 21.94 (q, J=6.17 Hz, 3C).

Workup

  1. customto give a colorless solution under nitrogen
  2. temperaturethe mixture was briefly warmed up to rt for 3 min
  3. temperatureAfter cooling down to −78° C.
  4. additionwas added via canuula
  5. stirringthe mixture was stirred for 2 h at −75° C
  6. customThe reaction was quenched with saturated sodium bicarbonate solution
  7. additiondiluted with ethyl acetate
  8. customThe layers were separated
  9. extractionThe aqueous layer was extracted with ethyl acetate
  10. washThe combined organic layers were washed with brine
  11. customdried
  12. concentrationconcentrated
  13. customto give a tan oil

Sources & evidence

ORD record
ord-ec31928b321240b4af0ca23b09fb7515
Source dataset
uspto-grants-2014_06
Patent number
US08748429B2

Linked notes

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