Hydrochloric Acid → HCID 68737059, compound

HRID 240767Notes

Reaction equation

HRID 240767 reaction equation
[CH2:1]([N:8]1[C:12]([CH2:13][NH:14][C:15](=[O:25])[CH2:16][NH:17]C(=O)OC(C)(C)C)=[C:11]([C:26]2[CH:27]=[C:28]3[C:32](=[CH:33][CH:34]=2)[NH:31][N:30]=[CH:29]3)[N:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl>O1CCCC1.C(OCC)C>[CH2:1]([N:8]1[C:12]([CH2:13][NH:14][C:15](=[O:25])[CH2:16][NH2:17])=[C:11]([C:26]2[CH:27]=[C:28]3[C:32](=[CH:33][CH:34]=2)[NH:31][N:30]=[CH:29]3)[N:10]=[N:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 68988005HCID 68988005, compound

Product 1

HCID 68737059HCID 68737059, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

Example 143C (66 mg, 0.217 mmol), N-(tert-butoxycarbonyl)-glycine (39 mg, 0.223 mmol), and HATU (85 mg, 0.224 mmol) were combined in methylene chloride (2.5 mL). Diisopropylethylamine (150 μL, 0.865 mmol) was added and the mixture was stirred at ambient temperature overnight. The mixture was absorbed on silica gel and purified by silica gel chromatography eluting with a gradient of 0-6% methanol in dichloromethane to afford tert-butyl 2-((1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazol-5-yl)methylamino)-2-oxoethylcarbamate. This carbamate was dissolved in tetrahydrofuran (2 mL) and 0.5 mL of a solution of 1 N hydrochloric acid in diethyl ether was added and the mixture was stirred for 20 minutes at room temperature. The solvents were removed under reduced pressure, and diethyl ether was added to the mixture and stirred at room temperature overnight. The solvent was decanted, and the resulting residue was dried under a stream of nitrogen to afford the title compound as a hydrochloride salt. 1H NMR (300 MHz, DMSO-d6) δ ppm 13.21 (s, 1H) 9.02 (t, J=5.09 Hz, 1H) 8.11-8.16 (m, 2H) 8.06 (s, 2H) 7.75-7.82 (m, 1H) 7.64 (d, J=8.82 Hz, 1H) 7.30-7.45 (m, 3H) 7.23-7.31 (m, 2H) 5.72 (s, 2H) 4.57 (d, J=5.09 Hz, 2H) 3.41 (q, J=5.76 Hz, 2H). MS (ESI+) m/z 362.1 (M+H)+.

Workup

  1. customThe solvents were removed under reduced pressure, and diethyl ether
  2. additionwas added to the mixture
  3. stirringstirred at room temperature overnight
  4. customThe solvent was decanted
  5. customthe resulting residue was dried under a stream of nitrogen

Sources & evidence

ORD record
ord-44c74143b25049cf9ab69a0a3f70f40e
Source dataset
uspto-grants-2014_02
Patent number
US08648069B2

Reaction notes

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