4-Phenoxypiperidine → 5-Bromo-3-nitro-4-(4-phenoxypiperidin-1-yl)pyridin-2-amine

HRID 416870Notes

Reaction equation

HRID 416870 reaction equation
[NH2:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6]([N:11]2[CH2:16][CH2:15]N(CC(NC3SC=CN=3)=O)[CH2:13][CH2:12]2)[C:5]([Br:26])=[CH:4][N:3]=1.BrC1C(Cl)=C([N+]([O-])=O)C(N)=NC=1.CCN(C(C)C)C(C)C.[O:48]([CH:55]1CCNCC1)[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1>C(O)(C)C>[Br:26][C:5]1[C:6]([N:11]2[CH2:12][CH2:13][CH:55]([O:48][C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[CH2:15][CH2:16]2)=[C:7]([N+:8]([O-:10])=[O:9])[C:2]([NH2:1])=[N:3][CH:4]=1

Participants

6

Reactant 4

HCID 188784-PhenoxypiperidineHCID 81531DiisopropylethylamineHCID 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)acetamide

Product 1

HCID 578971215-Bromo-3-nitro-4-(4-phenoxypiperidin-1-yl)pyridin-2-amineYield 84%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

This was prepared using the same procedure as for 2-(4-(2-amino-5-bromo-3-nitropyridin-4-yl)piperazin-1-yl)-N-(thiazol-2-yl)acetamide, but here using 5-bromo-4-chloro-3-nitropyridin-2-amine (162 mg, 0.64 mmol), DIPEA (3.5 eq, 2.24 mmol, 0.39 mL), isopropanol (3 mL) and 4-phenoxypiperidine (1.1 eq, 0.70 mmol, 125 mg). Concentration in vacuo to half volume after 18 h gave a bright yellow solid, which was filtered and washed with cold water (2×2 mL) to give the product (212 mg, 84%) as a yellow solid; δH (500 MHz, DMSO-d6) 1.74-1.81 (m, 2H, 2× piperidine CHAHB), 2.04-2.08 (m, br, 2H, 2× piperidine CHAHB), 2.98-3.03 (m, 2H, 2× piperidine NCHAHA), 3.24-3.27 (m, 2H, 2× piperidine NCHAHA), 4.63 (quintet, J=3.9 Hz, 1H, piperidine CH), 6.92 (t, J=7.4 Hz, 1H, phenyl H-6), 6.98 (s, br, 2H, NH2), 6.99 (d, J=7.8 Hz, 2H, phenyl H-2 & H-4), 7.28 (dd, J=8.6, 7.8 Hz, 2H, phenyl H-3 & H-5), 8.17 (s, 1H, pyridine H-6);

Workup

  1. customThis was prepared
  2. concentrationConcentration in vacuo to half volume after 18 h
  3. customgave a bright yellow solid, which
  4. filtrationwas filtered
  5. washwashed with cold water (2×2 mL)

Sources & evidence

ORD record
ord-377bb517b43e4dd79b43401ad1fb39a5
Source dataset
uspto-grants-2012_01
Patent number
US08088761B2

Reaction notes

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