Diisopropylethylamine → HCID 67205672, compound

HRID 384510Notes

Reaction equation

HRID 384510 reaction equation
Br[CH2:2][CH2:3][O:4][C:5]1[CH:20]=[CH:19][C:8]([O:9][C:10]2[S:11][C:12]3[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=3[N:14]=2)=[CH:7][CH:6]=1.[C:21]([O:25][C:26]([N:28]1[CH2:33][C@@H:32]2[CH2:34][C@H:29]1[CH2:30][NH:31]2)=[O:27])([CH3:24])([CH3:23])[CH3:22].C(N(C(C)C)CC)(C)C>CC#N>[C:21]([O:25][C:26]([N:28]1[CH2:33][C@@H:32]2[CH2:34][C@H:29]1[CH2:30][N:31]2[CH2:2][CH2:3][O:4][C:5]1[CH:20]=[CH:19][C:8]([O:9][C:10]2[S:11][C:12]3[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=3[N:14]=2)=[CH:7][CH:6]=1)=[O:27])([CH3:24])([CH3:22])[CH3:23]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptaneHCID 59989022HCID 59989022, compound

Product 1

HCID 67205672HCID 67205672, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 2-[4-(2-bromo-ethoxy)-phenoxy]-benzothiazole (1.5 g, 4.3 mmol) and (S,S)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (1.0 g, 5.1 mmol) in CH3CN (20 mL) at rt was added diisopropylethylamine ((i-Pr)2NEt) (900 μL, 5.1 mmol). The resulting suspension was stirred at rt for 4 h and then heated for 65 h at 60° C. The solution was cooled to rt and then partitioned between CH2Cl2 (200 mL) and satd. aq. NaHCO3 (80 mL). The organic layer was separated, dried (Na2SO4), filtered and concentrated. Purification by silica gel flash chromatography (0% to 5% CH3OH in CH2Cl2) afforded the title compound as a yellow oil (1.8 g, 92%). MS (ESI): mass calcd. for C25H29N3O4S, 467.19; m/z found, 468.1 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.75 (d, J=8.0 Hz, 1H), 7.68-7.66 (m, 1H), 7.42-7.38 (m, 1H), 7.31-7.25 (m, 3H), 6.99-6.95 (m, 2H), 4.40 (br s, 0.5H), 4.27 (br s, 0.5H), 4.13-4.03 (m, 2H), 3.66-3.51 (m, 2H), 3.26-2.97 (m, 4H), 2.78 (d, J=9.5 Hz, 0.5H), 2.63 (d, J=9.7 Hz, 0.5H), 1.92-1.85 (m, 1H), 1.79-1.70 (m, 1H), 1.49 (s, 9H).

Workup

  1. temperatureheated for 65 h at 60° C
  2. temperatureThe solution was cooled to rt
  3. custompartitioned between CH2Cl2 (200 mL)
  4. customThe organic layer was separated
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel flash chromatography (0% to 5% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-d8b67e904dae4ed595833de327b276e2
Source dataset
uspto-grants-2013_02
Patent number
US08367719B2

Reaction notes

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