2-Amino-6-methylpyridine → HCID 67237410, compound

HRID 2401516Notes

Reaction equation

HRID 2401516 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[N:11]([CH3:18])[C:12]1[CH:13]=[N:14][CH:15]=[N:16][CH:17]=1.[CH3:19][C:20]1[N:25]=[C:24]([NH2:26])[CH:23]=[CH:22][CH:21]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:26][C:24]2[CH:23]=[CH:22][CH:21]=[C:20]([CH3:19])[N:25]=2)=[O:8])=[CH:4][C:3]=1[N:11]([CH3:18])[C:12]1[CH:13]=[N:14][CH:15]=[N:16][CH:17]=1

Participants

6

Reactant 4

HCID 157652-Amino-6-methylpyridineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58318865HCID 58318865, compound

Product 1

HCID 67237410HCID 67237410, compoundYield 37.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Compound 20 (300 mg, 1.15 mmol, 1.00 eq) was dissolved in Dioxane (5.0 mL), and 1N LiOH (5.0 mL) was added. The reaction was stirred at rt for 45 minutes. The reaction was quenched with 1N HCl (5.0 mL) and extracted (3×) with ether. The combined organics were dried (MgSO4), filtered, and concentrated in vacuo to afford 200 mg (70%) of crude 4-fluoro-3-(methyl(pyrimidin-5-yl)amino)benzoic acid as a yellow solid. The product was confirmed by LCMS (>90% @ 220 nm and 254 nm) and carried forward without purification. 4-fluoro-3-(methyl(pyrimidin-5-yl)amino)benzoic acid (30 mg, 0.12 mmol, 1.0 eq), 6-methylpyridin-2-amine (15 mg, 0.14 mmol, 1.2 eq), O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (91 mg, 0.24 mmol, 2.0 eq), and N,N-Diisopropylethylamine (85 mg, 0.66 mmol, 5.5 eq) were dissolved in DMF (0.98 mL) and stirred at rt overnight. The reaction was quenched with water, and the layers were separated via phase separation. The organic layer was dried on air concentrator and purified by mass directed preparatory HPLC to afford 15 mg (36%) of the title compound as a mono-TFA salt: 1H NMR (400 MHz, DMSO-d6) δ 10.91 (s, 1H), 8.65 (s, 1H), 8.28 (s, 2H), 8.14 (dd, J=7.7, 2.2 Hz, 1H), 8.00-7.94 (m, 2H), 7.75 (t, J=7.9 Hz, 1H), 7.48 (dd, J=10.7, 8.7 Hz, 1H), 7.05 (dd, J=7.4, 1H), 3.39 (s, 3H), 2.45 (s, 3H); ES-MS [M+1]+:338.1.

Workup

  1. customcarried forward without purification
  2. customThe reaction was quenched with water
  3. customthe layers were separated via phase separation
  4. customThe organic layer was dried on air concentrator
  5. custompurified by mass

Sources & evidence

ORD record
ord-9a0928e4d7c24bb39b3d4a6501f977a7
Source dataset
uspto-grants-2014_08
Patent number
US08796295B2

Reaction notes

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