Methanol → HCID 178485253, compound

HRID 81252Notes

Reaction equation

HRID 81252 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:29][C@H:30]4[CH2:35][CH2:34][C@H:33]([CH3:36])[CH2:32][CH2:31]4)[C:15]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][C@H:18]4[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[N:16][C:12]=3[CH:11]=[C:10]([C:37]([OH:39])=O)[N:9]=2)[CH:5]=[N:6][CH:7]=1.[CH3:40][N:41](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CN.CO>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:29][C@H:30]4[CH2:31][CH2:32][C@H:33]([CH3:36])[CH2:34][CH2:35]4)[C:15]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][C@H:18]4[C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)=[N:16][C:12]=3[CH:11]=[C:10]([C:37]([NH:41][CH3:40])=[O:39])[N:9]=2)[CH:5]=[N:6][CH:7]=1

Participants

8

Reactant 5

HCID 887MethanolHCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178461226HCID 178461226, compound

Product 1

HCID 178485253HCID 178485253, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine-6-carboxylic acid (Example 3.22, prepared from Example 2.1, Step 4 using a procedure similar to that described for Example 1.1, Step 5; 50 mg, 0.09 mmol) in DMF (2.0 mL) were added HATU (15 mg, 0.11 mmol), DIPEA (0.03 mL, 0.18 mmol), and 2.0 M methylamine in MeOH (0.09 mL, 0.18 mmol) at room temperature. After being stirred for 2 hours, the reaction mixture was diluted with H2O (10 mL), the aqueous layer was extracted with EtOAc and then the organic layer was washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Purification of the residue on a silica gel column (0 to 10% MeOH/CH2Cl2) afforded 4-(5-chloropyridin-3-yl)-N-methyl-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine-6-carboxamide. 1H NMR (300 MHz, CD3OD) δ 8.71 (d, J=2.1 Hz, 1H), 8.66 (s, 1H), 8.17-8.19 (m, 2H) 7.40-7.42 (m, 2H), 7.24-7.26 (m, 3H), 4.66-4.69 (m, 1H), 3.98-4.06 (m, 4H), 3.66-3.75 (m, 2H), 3.41-3.50 (m, 2H), 3.48 (s, 3H), 1.28-1.43 (m, 2H), 1.10-1.19 (m, 1H), 0.82-0.99 (m, 2H), 0.74 (d, J=6.3 Hz, 3H) 0.61-0.65 (m, 3H), 0.41-0.45 (m, 2H). MS APCl calc'd. for C31H35ClN6O2 [M+H]+ 559. found 559.

Workup

  1. extractionthe aqueous layer was extracted with EtOAc
  2. washthe organic layer was washed with water and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue on a silica gel column (0 to 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-1ce58f06b74e418dae6e02e360c42a3d
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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