Methyl iodide → HCID 46195843, compound

HRID 1877360Notes

Reaction equation

HRID 1877360 reaction equation
[Cl:1][C:2]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:3]=1[O:4][C:5]1[N:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=O.[Cl:19][C:20]1[C:25]([NH2:26])=[C:24]([CH3:27])[CH:23]=[CH:22][N:21]=1.[CH2:28](N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[H-].[Na+].IC>CN(C=O)C>[Cl:19][C:20]1[C:25]([N:26]([CH3:28])[C:7](=[O:9])[C:6]2[CH:10]=[CH:11][CH:12]=[N:13][C:5]=2[O:4][C:3]2[CH:14]=[C:15]([Cl:18])[CH:16]=[CH:17][C:2]=2[Cl:1])=[C:24]([CH3:27])[CH:23]=[CH:22][N:21]=1

Participants

8

Reactant 6

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 81531DiisopropylethylamineHCID 27563873-Amino-2-chloro-4-methylpyridineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 167959962-(2,5-Dichloro-phenoxy)-nicotinic acid

Product 1

HCID 46195843HCID 46195843, compoundYield 3.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(2,5-dichloro-phenoxy)-nicotinic acid (56.6 mg, 0.2 mmol, 1.0 equiv; Example 31, Step 1) in anhydrous DMF (1 mL) was added 2-chloro-4-methyl-pyridin-3-ylamine (34.2 mg, 0.24 mmol, 1.2 equiv; [CAS RN 133627-45-9]), N-ethyldiisopropylamine (129.0 mg, 175 μL, 1.0 mmol, 5.0 equiv; [CAS RN 7087-68-5]) and HATU (91.2 mg, 0.24 mmol, 1.2 equiv; [CAS RN 148893-10-1]) and the reaction mixture stirred at rt. After 18 h, sodium hydride (13.0 mg, 0.3 mmol, 1.5 equiv; 55% free-flowing powder moistened with oil; [CAS RN 7646-69-7]) and iodomethane (56.8 mg, 25 μL, 0.4 mmol, 2.0 equiv; [CAS RN 74-88-4]) were added and stirring continued at 40° C. for 2 h. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 2.9 mg (3%) of the title compound. MS (ISP): 424.1 [M+H]+.

Workup

  1. stirringstirring
  2. waitcontinued at 40° C. for 2 h
  3. customRemoval of the solvent mixture
  4. customunder reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column
  5. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
  6. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

Sources & evidence

ORD record
ord-6bdbea3892e94cbfa087494c6e1ef801
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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