5-Bromo-4-chloro-3-nitropyridin-2-amine → 5-Bromo-3-nitro-4-(4-(1-(pyridin-2-yl)ethyl)piperazin-1-yl)pyridin-2-amine

HRID 416772Notes

Reaction equation

HRID 416772 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]([N:9]1[CH2:14][CH2:13][N:12]([C:15](OC(C)(C)C)=O)[CH2:11][CH2:10]1)[CH3:8].[Br:22][C:23]1C(Cl)=[C:25]([N+:30]([O-:32])=[O:31])[C:26]([NH2:29])=[N:27][CH:28]=1.NC1C([N+]([O-])=O)=C(N2CCN(CC(NC3SC=CN=3)=O)CC2)C(Br)=CN=1>C(O)(C(F)(F)F)=O.C(Cl)Cl.CC(O)C.CCN(C(C)C)C(C)C>[Br:22][C:23]1[C:15]([N:12]2[CH2:11][CH2:10][N:9]([CH:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[CH3:8])[CH2:14][CH2:13]2)=[C:25]([N+:30]([O-:32])=[O:31])[C:26]([NH2:29])=[N:27][CH:28]=1

Participants

8

Reactant 3

HCID 454802365-Bromo-4-chloro-3-nitropyridin-2-amineHCID 468678032-(4-(2-amino-5-bromo-3-nitropyridin-4-yl)piperazin-1-yl)-N-(thiazol-2-yl)acetamideHCID 60137623tert-Butyl 4-(1-(pyridin-2-yl)ethyl)piperazine-1-carboxylate

Product 1

HCID 578971485-Bromo-3-nitro-4-(4-(1-(pyridin-2-yl)ethyl)piperazin-1-yl)pyridin-2-amine

Reagents, catalysts & solvents 4

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolventHCID 81531DiisopropylethylamineSolvent

Procedure

A solution of tert-butyl 4-(1-(pyridin-2-yl)ethyl)piperazine-1-carboxylate (1.1 eq, 1.10 mmol, 321 mg) in TFA (4 mL) and CH2Cl2 (4 mL) at 0° C. was stirred for 30 minutes and concentrated in vacuo. The remaining TFA was removed by azeotroping with toluene (3×10 mL) and drying at high vacuum for 2 h. Then the residue was reacted with 5-bromo-4-chloro-3-nitropyridin-2-amine (253 mg, 1.00 mmol) in iPrOH (5 mL) and DIPEA (2 mL) using the same procedure described for 2-(4-(2-amino-5-bromo-3-nitropyridin-4-yl)piperazin-1-yl)-N-(thiazol-2-yl)acetamide. After 18 h, the precipitate was filtered and washed with cold water (2×3 mL) and hexane (3 mL) to give the product (313 mg, 70% for two steps) as a yellow solid; 1H-NMR (500 MHz, DMSO-d6) 1.33 (d, J=6.7 Hz, 3H, CH3), 2.48-2.62 (2 m, 4H, piperazine N(CH2)2), 3.04-3.13 (m, 4H, piperazine N(CH2)2), 3.63-3.69 (m, 1H, CH), 6.95 (br s, 2H, NH2), 7.25 (dd, br, J=6.8, 5.2 Hz, 1H, pyridine H-5), 7.44 (d, J=7.8 Hz, 1H, pyridine H-3), 7.77 (td, J=7.7, 1.6 Hz, 1H, pyridine H-4), 8.13 (s, 1H, bromopyridine H-6), 8.50 (d, br, J=4.2 Hz, 1H, pyridine H-6);

Workup

  1. concentrationconcentrated in vacuo
  2. customThe remaining TFA was removed
  3. customby azeotroping with toluene (3×10 mL)
  4. customdrying at high vacuum for 2 h
  5. filtrationthe precipitate was filtered
  6. washwashed with cold water (2×3 mL) and hexane (3 mL)
  7. customto give the product (313 mg, 70% for two steps) as a yellow solid

Sources & evidence

ORD record
ord-534d8b670c5244bdb6dcfe63d48e7dbc
Source dataset
uspto-grants-2012_01
Patent number
US08088761B2

Reaction notes

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