Cyclopropylamine → HCID 86707740, compound

HRID 1190847Notes

Reaction equation

HRID 1190847 reaction equation
O=C1[N:6]([S:7]([NH:10][C@@H:11]([CH2:22][C:23]2[O:24][C:25]([CH2:28][C:29]3[S:30][C:31]4[CH:37]=[C:36]([C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=5)[CH:35]=[CH:34][C:32]=4[N:33]=3)=[N:26][N:27]=2)[C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])(=[O:9])=[O:8])[CH2:5][CH2:4]O1.[CH:44]1(N)CC1>C(#N)C>[CH:5]1([NH:6][S:7]([NH:10][C@@H:11]([CH2:22][C:23]2[O:24][C:25]([CH2:28][C:29]3[S:30][C:31]4[CH:37]=[C:36]([C:38]5[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=5)[CH:35]=[CH:34][C:32]=4[N:33]=3)=[N:26][N:27]=2)[C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])(=[O:8])=[O:9])[CH2:4][CH2:44]1

Participants

4

Reactant 2

HCID 69828CyclopropylamineHCID 86707741HCID 86707741, compound

Product 1

HCID 86707740HCID 86707740, compoundYield 46.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 2-chloroethanol (0.10 mL, 1.3 mmol) in DCM (1 mL) at rt was added a solution of sulfurisocyanatidic chloride (180 mg, 1.3 mmol) in DCM (1 mL) and the reaction mixture was stirred for 6 h. The resulting mixture was added to a solution of Compound 181a (300 mg, 0.65 mmol, prepared as described in Example 45) and TEA (0.45 mL, 3.2 mmol) in DCM (4 mL) and the mixture stirred for 30 min then heated at 35° C. for 16 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with 0-100% hexane/EtOAc to afford (S)-benzyl 2-(2-oxooxazolidine-3-sulfonamido)-3-(5-((6-phenylbenzo[d]thiazol-2-yl)methyl)-1,3,4-oxadiazol-2-yl)propanoate (230 mg, 57% yield) as a yellow foam. LCMS=1.2 min using analytical method (B), 620.2 (M+H). A portion of (S)-benzyl 2-(2-oxooxazolidine-3-sulfonamido)-3-(5-((6-phenylbenzo[d]thiazol-2-yl)methyl)-1,3,4-oxadiazol-2-yl)propanoate (93 mg, 0.15 mmol) was dissolved in ACN (3 mL) then TEA (0.031 mL, 0.23 mmol) was added followed by cyclopropanamine (0.053 mL, 0.75 mmol) and the reaction mixture heated at 70° C. for 16 h. The reaction mixture was allowed to cool to rt then concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0-100% hexane/EtOAc to give Compound 181b (41 mg, 46% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.13-7.97 (m, 2H), 7.72 (dd, J=8.5, 1.9 Hz, 1H), 7.67-7.59 (m, 2H), 7.51-7.44 (m, 2H), 7.42-7.38 (m, 1H), 7.34-7.31 (m, 3H), 7.30-7.27 (m, 2H), 5.53 (d, J=8.1 Hz, 1H), 5.23 (s, 1H), 5.18 (s, 2H), 4.68 (d, J=4.4 Hz, 2H), 3.43 (dd, J=5.7, 1.8 Hz, 2H), 2.51-2.35 (m, 1H), 0.65-0.43 (m, 4H). LCMS=1.2 min using analytical method (B), 590.2 (M+H)±.

Workup

  1. customLCMS=1.2 min
  2. temperatureto cool to rt
  3. concentrationthen concentrated under reduced pressure
  4. customThe residue was purified by silica gel chromatography
  5. washeluting with 0-100% hexane/EtOAc

Sources & evidence

ORD record
ord-18b318b616134f91be595476b2e49fc1
Source dataset
uspto-grants-2014_03
Patent number
US08680090B2

Reaction notes

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