Triethylamine → (S,S)-{5-[4-(Benzothiazol-2-yloxy)-benzyl]-2,5-diaza-bicyclo[2.2.1]hept-2-yl}-acetic acid tert-butyl ester

HRID 1799074Notes

Reaction equation

HRID 1799074 reaction equation
Cl.[C@H:2]12[CH2:8][C@H:5]([NH:6][CH2:7]1)[CH2:4][N:3]2[CH2:9][C:10]1[CH:25]=[CH:24][C:13]([O:14][C:15]2[S:16][C:17]3[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=3[N:19]=2)=[CH:12][CH:11]=1.[C:26]([O:30][C:31](=[O:34])[CH2:32]Br)([CH3:29])([CH3:28])[CH3:27].CCN(CC)CC>CC#N>[C:26]([O:30][C:31](=[O:34])[CH2:32][N:6]1[CH2:7][C@@H:2]2[CH2:8][C@H:5]1[CH2:4][N:3]2[CH2:9][C:10]1[CH:11]=[CH:12][C:13]([O:14][C:15]2[S:16][C:17]3[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=3[N:19]=2)=[CH:24][CH:25]=1)([CH3:29])([CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 79177tert-Butyl bromoacetateHCID 67207143(S,S)-2-[4-(2,5-diaza-bicyclo[2.2.1]hept-2-ylmethyl)-phenoxy]-benzothiazole hydrochloride

Product 1

HCID 67207820(S,S)-{5-[4-(Benzothiazol-2-yloxy)-benzyl]-2,5-diaza-bicyclo[2.2.1]hept-2-yl}-acetic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of (S,S)-2-[4-(2,5-diaza-bicyclo[2.2.1]hept-2-ylmethyl)-phenoxy]-benzothiazole hydrochloride (257 mg, 0.63 mmol) and bromoacetic acid tert-butyl ester (110 μL, 0.75 mmol) in CH3CN (4.0 mL) at rt was added Et3N (270 μL, 1.9 mmol). After 18 h at rt, the suspension was 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 (5% CH3OH in CH2Cl2) afforded the title compound as a viscous, colorless oil (218 mg, 77%). MS (ESI): mass calcd. for C25H29N3O3S, 451.19; m/z found, 452.2 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.75 (d, J=7.7 Hz, 1H), 7.67 (d, J=7.7 Hz, 1H), 7.44 (d, J=8.6 Hz, 2H), 7.39 (m, 1H), 7.34-7.25 (m, 3H), 3.75 (m, 2H), 3.43 (br s, 1H), 3.33 (m, 3H), 2.88 (m, 2H), 2.82 (br d, J=10.0 Hz, 1H), 2.70 (dd, J=10.0, 2.2 Hz, 1H), 1.78 (s, 2H), 1.48 (s, 9H).

Workup

  1. customthe suspension was partitioned between CH2Cl2 (200 mL)
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by silica gel flash chromatography (5% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-0faddebeee58406e8035df9b6a313d2b
Source dataset
uspto-grants-2013_01
Patent number
US08344008B2

Reaction notes

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