Hydrochloric Acid → HCID 70978096, compound

HRID 2281074Notes

Reaction equation

HRID 2281074 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][CH:12]3[CH2:14][CH2:13]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[C:15]1[CH:34]=[CH:33][C:18]([CH2:19][N:20]2[CH2:25][CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22][CH2:21]2)=[CH:17][CH:16]=1.Cl.C(=O)(O)[O-].[Na+]>ClCCl.CO.O>[Cl:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][CH:12]3[CH2:14][CH2:13]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[C:15]1[CH:16]=[CH:17][C:18]([CH2:19][N:20]2[CH2:21][CH2:22][NH:23][CH2:24][CH2:25]2)=[CH:33][CH:34]=1

Participants

7

Reactant 3

HCID 313Hydrochloric Acid2×HCID 516892Sodium BicarbonateHCID 71002317HCID 71002317, compound

Product 1

HCID 70978096HCID 70978096, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

tert-Butyl 4-{4-[4-chloro-1-(cyclopropylmethyl)-1H-benzotriazol-5-yl]benzyl}piperazine-1-carboxylate (Example 52, 430 mg, 0.89 mmol) was dissolved in a dichloromethane (8.9 mL) and methanol (8.9 mL), cooled to 0° C. and treated with a hydrochloric acid (2.2 mL, 4 M in dioxane, 8.9 mmol). The mixture was warmed to ambient temperature and treated with hydrochloric acid (200 μL, 12 N aqueous). The mixture was stirred at ambient temperatures until complete, at which time the mixture was treated with aqueous saturated sodium bicarbonate, diluted with water and extracted with ethyl acetate (3×40 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (100:0 to 90:5; dichloromethane:methanol) to afford the product as a clear oil: 1H-NMR (400 MHz, CDCl3) δ 7.51 (1H, d, J=1.9 Hz); 7.48-7.42 (5H, m); 4.56 (2H, d, J=7.0 Hz); 3.57 (2H, s); 2.93 (5H, t, J=4.8 Hz); 2.81 (3H, t, J=4.8 Hz); 1.49-1.38 (1H, m); 0.73-0.65 (2H, m); 0.57-0.48 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 382.1796 [(M+H)+; calculated for C21H25ClN5: 382.1793].

Workup

  1. temperatureThe mixture was warmed to ambient temperature
  2. extractionextracted with ethyl acetate (3×40 mL)
  3. dry with materialThe combined organic extracts were dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography (100:0 to 90:5; dichloromethane:methanol)

Sources & evidence

ORD record
ord-8bb604c38d4f45dab41787efb36bc564
Source dataset
uspto-grants-2015_09
Patent number
US09139576B2

Reaction notes

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