1H-Imidazo(4,5-c)pyridine → N-((R)-8-fluorochroman-4-yl)-2-(3H-imidazo[4,5-c]pyridin-3-yl)-5-nitropyrimidin-4-amine

HRID 605843Notes

Reaction equation

HRID 605843 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@H:9]2[C:18]3[C:13](=[C:14]([F:19])[CH:15]=[CH:16][CH:17]=3)[O:12][CH2:11][CH2:10]2)[C:5]([N+:20]([O-:22])=[O:21])=[CH:4][N:3]=1.[N:23]1[C:31]2[CH:30]=[CH:29][N:28]=[CH:27][C:26]=2[NH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.CCOC(C)=O>[F:19][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:13]=1[O:12][CH2:11][CH2:10][C@H:9]2[NH:8][C:6]1[C:5]([N+:20]([O-:22])=[O:21])=[CH:4][N:3]=[C:2]([N:25]2[C:26]3[CH:27]=[N:28][CH:29]=[CH:30][C:31]=3[N:23]=[CH:24]2)[N:7]=1

Participants

6

Reactant 3

HCID 92271H-Imidazo(4,5-c)pyridineHCID 11430Potassium CarbonateHCID 59704905(R)-2-chloro-N-(8-fluorochroman-4-yl)-5-nitropyrimidin-4-amine

Product 1

HCID 59705035N-((R)-8-fluorochroman-4-yl)-2-(3H-imidazo[4,5-c]pyridin-3-yl)-5-nitropyrimidin-4-amine

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (R)-2-chloro-N-(8-fluorochroman-4-yl)-5-nitropyrimidin-4-amine in acetonitrile was treated with 3H-imidazo[4,5-c]pyridine and potassium carbonate. The mixture was stirred at reflux for 6 hours, cooled to room temperature, diluted with 150 mL of EtOAc, and washed twice with 30 mL portions of water. The organic layer was separated, dried with magnesium sulfate, filtered, and concentrated in vacuo. Purification by column chromatography (1% MeOH/DCM) provided N—((R)-8-fluorochroman-4-yl)-2-(3H-imidazo[4,5-c]pyridin-3-yl)-5-nitropyrimidin-4-amine as the first eluting isomer: (1H-NMR (300 MHz, CDCl3) δ 9.8 (s, 1H), 9.4 (s, 1H), 9.2 (s, 1H), 8.9 (d, 1H), 8.6 (d, 1H), 7.8 (d, 1H), 7.1 (m, 2H), 6.9 (m, 1H), 5.8 (q, 1H), 4.6 (m, 1H), 4.4 (m, 1H), 2.6 (m, 1H), 2.4 (m, 1H).). N—((R)-8-Fluorochroman-4-yl)-2-(1H-imidazo[4,5-c]pyridin-1-yl)-5-nitropyrimidin-4-amine eluted second: (1H-NMR (300 MHz, CDCl3) δ 9.4 (s, 1H), 9.2 (s, 1H), 9.1 (s, 1H), 8.9 (d, 1H), 8.6 (d, 1H), 8.4 (d, 1H), 7.1 (m, 2H), 6.9 (m, 1H), 5.7 (q, 1H), 4.5 (m, 1H), 4.4 (m, 1H), 2.6 (m, 1H), 2.4 (m, 1H).).

Workup

  1. temperatureat reflux for 6 hours
  2. washwashed twice with 30 mL portions of water
  3. customThe organic layer was separated
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by column chromatography (1% MeOH/DCM)

Sources & evidence

ORD record
ord-3ef9143243fa4d1a89655e93e8cda578
Source dataset
uspto-grants-2011_03
Patent number
US07915268B2

Reaction notes

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