2-Chloronicotinic acid → HCID 11249794, compound

HRID 2353033Notes

Reaction equation

HRID 2353033 reaction equation
[OH:1][CH2:2][CH:3]1[CH:7]2[O:8][C:9]([CH3:12])([CH3:11])[O:10][CH:6]2[CH:5]([N:13]2[CH:21]=[N:20][C:19]3[C:14]2=[N:15][CH:16]=[N:17][C:18]=3[NH:22][C:23]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:24])[O:4]1.CC(C)([O-])C.[K+].Cl[C:39]1[N:47]=[CH:46][CH:45]=[CH:44][C:40]=1[C:41]([OH:43])=[O:42]>CN(C=O)C>[CH3:12][C:9]1([CH3:11])[O:10][CH:6]2[CH:5]([N:13]3[CH:21]=[N:20][C:19]4[C:14]3=[N:15][CH:16]=[N:17][C:18]=4[NH:22][C:23]([NH:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[O:24])[O:4][CH:3]([CH2:2][O:1][C:39]3[N:47]=[CH:46][CH:45]=[CH:44][C:40]=3[C:41]([OH:43])=[O:42])[CH:7]2[O:8]1

Participants

5

Reactant 3

HCID 762582-Chloronicotinic acidHCID 23665647Potassium tert-butoxideHCID 67150697HCID 67150697, compound

Product 1

HCID 11249794HCID 11249794, compoundYield 27.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
23 °C

Procedure

To a stirred solution of 1-[9-(6-hydroxymethyl-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl)-9H-purin-6-yl]-3-phenyl-urea (43 mg, 0.1 mmol) in dry N,N′-dimethylformamide (1 mL) at 23° C. was added potassium tert-butoxide (45 mg, 0.4 mmol). After 30 min, 2-chloronicotinic acid (60 mg, 0.4 mmol) was added to the solution. The resulting mixture was stirred at 23° C. for 15 h and then quenched with water (1 mL), suspended in ethyl acetate (50 mL), washed with brine (3×), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give the crude product. Preparative reverse-phase HPLC was used to obtain the pure compound (15 mg, 27% yield) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 11.76 (s, 1H), 10.15 (s, 1H), 9.16 (s, 1H), 8.65 (s, 1H), 8.05 (dd, J=8.5 Hz, 3.5 Hz, 1H), 7.94 (dd, J=9.0 Hz, 3.0 Hz, 1H), 7.60 (d, J=2.0 Hz, 1H), 7.57 (d, J=2.0 Hz, 1H), 7.32 (t, J=12.5 Hz, 2H), 7.05 (t, J=12.5 Hz, 1H), 6.96 (dd, J=12.5 Hz, 8.5 Hz, 1H), 6.25 (d, J=6.0 Hz, 1H), 5.80 (t, J=7.5 Hz, 1H), 5.10 (dd, J=9.0 Hz, 2.5 Hz, 1H), 4.67 (m, 1H), 4.53 (dd, J=20.0 Hz, 4.0 Hz, 1H), 4.36 (dd, J=20.0 Hz, 4.0 Hz, 1H), 1.59 (s, 3H), 1.38 (s, 3H). MW calculated for C26H25N7O7 (MH+) 548. found 548 by LCMS. Similarly, other 5′-substituted pyridines were prepared:

Workup

  1. customquenched with water (1 mL)
  2. washwashed with brine (3×)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give the crude product

Sources & evidence

ORD record
ord-fefecfd0ec894921bab874a40257f40d
Source dataset
uspto-grants-2010_07
Patent number
US07749981B2

Reaction notes

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