Hydrochloric Acid → HCID 178457305, compound

HRID 2061630Notes

Reaction equation

HRID 2061630 reaction equation
Cl.C(O[C:7](=[O:28])[NH:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([CH2:15][CH2:16][NH:17][C@H:18]2[CH2:27][CH2:26][C:21]3[N:22]=[C:23]([NH2:25])[S:24][C:20]=3[CH2:19]2)[CH2:11][CH2:10]1)(C)(C)C.C(O)(=O)[CH:30]=[CH:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.CCN=C=N[CH2:45][CH2:46][CH2:47]N(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>O1CCOCC1.C1COCC1>[NH2:25][C:23]1[S:24][C:20]2[CH2:19][C@@H:18]([N:17]([CH2:45][CH2:46][CH3:47])[CH2:16][CH2:15][C@H:12]3[CH2:11][CH2:10][C@H:9]([NH:8][C:7](=[O:28])[CH:30]=[CH:31][C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH2:14][CH2:13]3)[CH2:27][CH2:26][C:21]=2[N:22]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 87842-Propenoic acid, 3-phenyl-HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 178453921HCID 178453921, compound

Product 1

HCID 178457305HCID 178457305, compoundYield 80.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent2×

Procedure

4.0 M HCl solution in dioxane (1.0 mL, 4.0 mmol) was added to a solution of compound 20 (87 mg, 0.2 mmol) in dioxane (10 mL) and the reaction mixture was stirred at room temperature for 2 hours. Solvent was evaporated in vacuo and the residue was used directly for the next step without further purification. To a solution of the residue in THF (20 mL) were added cinnamic acid (29 mg, 0.2 mmol), EDCI (38 mg, 0.2 mmol), HOBT (27 mg, 0.2 mmol), and DIPEA (103 mg, 0.8 mmol). The reaction mixture was stirred at room temperature for 2 hours. Solvent was evaporated in vacuo. The residue was partitioned between ethyl acetate and water. The organic layer was separated and washed with brine, and dried over anhydrous Na2SO4. Flash column chromatography (MeOH/EtOAc, 1:6) gave compound 12 as a colorless oil (75 mg, 80%). 1H NMR (CDCl3, 300 MHz) δ 7.63 (d, J=15.6 Hz, 1H, 7.52-7.35 (m, 5H), 6.39 (d, J=15.6 Hz, 1H), 5.60 (s, broad, 1H), 4.90 (s, 2H), 3.95-3.80 (m, 1H), 3.30-2.30 (m, 8H), 2.20-1.95 (m, 3H), 1.93-1.02 (m, 13H), 0.92 (t, J=6.6 Hz, 3H); 13C NMR (CDCl3, 75 MHz) δ 165.87, 165.05, 144.85, 140.66, 134.92, 129.54, 128.77, 127.73, 121.10, 69.73, 57.86, 52.54, 48.71, 35.18, 33.06, 31.80, 30.84, 26.34, 25.36, 24.76, 18.88, 11.79; HRMS-Electrospray (m/z): [M+H]+ calcd 467.2845. found 467.2830; purity HPLC 95.4%, tR=29.227 min.

Workup

  1. customSolvent was evaporated in vacuo
  2. customthe residue was used directly for the next step without further purification
  3. stirringThe reaction mixture was stirred at room temperature for 2 hours
  4. customSolvent was evaporated in vacuo
  5. customThe residue was partitioned between ethyl acetate and water
  6. customThe organic layer was separated
  7. washwashed with brine
  8. dry with materialdried over anhydrous Na2SO4

Sources & evidence

ORD record
ord-7b63ae4524644f33be039e3b834480bc
Source dataset
uspto-grants-2012_10
Patent number
US08283368B2

Reaction notes

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