Hydrochloric Acid → HCID 178457304, compound

HRID 2061629Notes

Reaction equation

HRID 2061629 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.[O:29]1[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[CH:31]=[C:30]1C(O)=O.C(N=C=N[CH2:46][CH2:47][CH2:48]N(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>O1CCOCC1.O1CCCC1>[NH2:25][C:23]1[S:24][C:20]2[CH2:19][C@@H:18]([N:17]([CH2:46][CH2:47][CH3:48])[CH2:16][CH2:15][C@H:12]3[CH2:11][CH2:10][C@H:9]([NH:8][C:7]([C:30]4[O:29][C:33]5[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=5[CH:31]=4)=[O:28])[CH2:14][CH2:13]3)[CH2:27][CH2:26][C:21]=2[N:22]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 10331Benzofuran-2-carboxylic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 178453921HCID 178453921, compound

Product 1

HCID 178457304HCID 178457304, compoundYield 63%

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 tetrahydrofuran (THF) (20 mL), were added benzofuran-2-carboxylic acid (32 mg, 0.2 mmol), 1-ethyl-3(3-dimethylaminopropyl)carbodiimide (EDCI) (38 mg, 0.2 mmol), 1-hydroxybenzotriazole (HOBT) (27 mg, 0.2 mmol), and diisopropylethylamine (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 11 as a colorless oil (60 mg, 63%). 1H NMR (CDCl3, 300 MHz) δ 7.68 (d, 7.6 Hz, 1H), 7.52-7.28 (m, 4H), 6.49 (d, J=8.2 Hz, 1H), 4.82 (s, broad, 2H), 3.98-3.85 (m, 1H), 3.50-2.25 (m, 8H), 2.20-1.10 (m, 16H), 0.94 (t, J=6.6 Hz, 3H); 13C NMR (CDCl3, 75 MHz) δ 158.50, 155.06, 149.22, 128.06, 127.22, 124.08, 123.11, 112.08, 110.71, 52.80, 48.68, 35.63, 33.04, 31.74, 19.26, 11.97, 11.77; HRMS-Electrospray (m/z): [M+H]+ calcd 481.2637. found 481.2637; purity HPLC 99.2%, tR=29.761 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-ba9d7f5403594606a55345544ac564f2
Source dataset
uspto-grants-2012_10
Patent number
US08283368B2

Reaction notes

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