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

HRID 416876Notes

Reaction equation

HRID 416876 reaction equation
BrC1C(N2CCN(C(C3C=CC=CN=3)C)CC2)=C([N+]([O-])=O)C(N)=NC=1.[N:26]1[CH:31]=[C:30]([CH2:32][N:33]2[CH2:38][CH2:37][N:36]([C:39](OC(C)(C)C)=O)[CH2:35][CH2:34]2)[CH:29]=[N:28][CH:27]=1.C(O)(C(F)(F)F)=O.ClC1[C:59]([Cl:60])=[CH:58][N:57]=[C:56]([NH2:61])[C:55]=1[N+:62]([O-:64])=[O:63]>CC(O)C.CCN(C(C)C)C(C)C.C(Cl)Cl>[Cl:60][C:59]1[C:39]([N:36]2[CH2:35][CH2:34][N:33]([CH2:32][C:30]3[CH:29]=[N:28][CH:27]=[N:26][CH:31]=3)[CH2:38][CH2:37]2)=[C:55]([N+:62]([O-:64])=[O:63])[C:56]([NH2:61])=[N:57][CH:58]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 46867017Tert-butyl 4-(pyrimidin-5-ylmethyl)piperazine-1-carboxylateHCID 468676602-Amino-4,5-dichloro-3-nitropyridineHCID 578971485-Bromo-3-nitro-4-(4-(1-(pyridin-2-yl)ethyl)piperazin-1-yl)pyridin-2-amine

Product 1

HCID 578972615-Chloro-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, 0.13 mmol, 35 mg), TFA (0.25 mL) and CH2Cl2 (1 mL), then 4,5-dichloro-3-nitropyridin-2-amine (37 mg, 0.11 mmol) in iPrOH (1 mL) and DIPEA (0.25 mL). Filtration and washing as previously described gave the product (22 mg, 50% for two steps) as a yellow solid; δH (500 MHz, DMSO-d6) 2.52 (s, br, 4H, piperazine N(CH2)2), 3.07 (t, J=4.5 Hz, 4H, piperazine N(CH2)2), 3.60 (s, 2H, CH2), 6.95 (s, br, 2H, NH2), 8.06 (s, 1H, pyridine 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 (22 mg, 50% for two steps) as a yellow solid

Sources & evidence

ORD record
ord-2d4a11b4869f43e9a92db75e39c9121e
Source dataset
uspto-grants-2012_01
Patent number
US08088761B2

Reaction notes

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