Trifluoroacetic acid → 5-Bromo-3-nitro-4-(4-(pyrimidin-5-ylmethyl)piperazin-1-yl)pyridin-2-amine

HRID 416856Notes

Reaction equation

HRID 416856 reaction equation
[Br:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][N:15]([CH:18](C3C=CC=CN=3)C)[CH2:14][CH2:13]2)=[C:4]([N+:9]([O-:11])=[O:10])[C:5]([NH2:8])=[N:6][CH:7]=1.[N:26]1[CH:31]=[C:30](CN2CCN(C(OC(C)(C)C)=O)CC2)[CH:29]=[N:28][CH:27]=1.C(O)(C(F)(F)F)=O.BrC1C(Cl)=C([N+]([O-])=O)C(N)=NC=1>CC(O)C.CCN(C(C)C)C(C)C.C(Cl)Cl>[Br:1][C:2]1[C:3]([N:12]2[CH2:13][CH2:14][N:15]([CH2:18][C:30]3[CH:31]=[N:26][CH:27]=[N:28][CH:29]=3)[CH2:16][CH2:17]2)=[C:4]([N+:9]([O-:11])=[O:10])[C:5]([NH2:8])=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 454802365-Bromo-4-chloro-3-nitropyridin-2-amineHCID 46867017Tert-butyl 4-(pyrimidin-5-ylmethyl)piperazine-1-carboxylateHCID 578971485-Bromo-3-nitro-4-(4-(1-(pyridin-2-yl)ethyl)piperazin-1-yl)pyridin-2-amine

Product 1

HCID 468687805-Bromo-3-nitro-4-(4-(pyrimidin-5-ylmethyl)piperazin-1-yl)pyridin-2-amine

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolventHCID 81531DiisopropylethylamineSolvent

Procedure

This was prepared using the same procedure as for 5-bromo-3-nitro-4-(4-(1-(pyridin-2-yl)ethyl)piperazin-1-yl)pyridin-2-amine, but here using tert-butyl 4-(pyrimidin-5-ylmethyl)piperazine-1-carboxylate (1.1 eq, 0.37 mmol, 104 mg), TFA (1.5 mL) and CH2Cl2 (4 mL), then 5-bromo-4-chloro-3-nitropyridin-2-amine (86 mg, 0.34 mmol) in iPrOH (3 mL) and DIPEA (0.75 mL). Filtration and washing as previously described gave the product (99 mg, 67% for two steps) as a yellow solid; δH (500 MHz, DMSO-d6) 2.54 (s, br, 4H, piperazine N(CH2)2), 3.06 (s, br, 4H, piperazine N(CH2)2), 3.60 (s, 2H, NCH2), 6.97 (s, br, 2H, NH2), 8.16 (s, 1H, bromopyridine H-6), 8.75 (s, 2H, pyrimidine H-4 & H-6), 9.10 (s, 1H, pyrimidine H-2);

Workup

  1. customThis was prepared
  2. filtrationFiltration
  3. washwashing
  4. customas previously described gave the product (99 mg, 67% for two steps) as a yellow solid

Sources & evidence

ORD record
ord-72b0943085e647009ad0105ee10e5e8e
Source dataset
uspto-grants-2012_01
Patent number
US08088761B2

Reaction notes

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