Diisopropylethylamine → N-(4-tert-Butyl-6-methyl-pyridin-2-yl)-2-[2-fluoro-4-(7-pyridin-4-yl-imidazo[1,2-a]pyridin-3-yl)-phenyl]-acetamide

HRID 1446725Notes

Reaction equation

HRID 1446725 reaction equation
Cl.Cl.[F:3][C:4]1[CH:9]=[C:8]([C:10]2[N:14]3[CH:15]=[CH:16][C:17]([C:19]4[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=4)=[CH:18][C:13]3=[N:12][CH:11]=2)[CH:7]=[CH:6][C:5]=1[CH2:25][C:26]([OH:28])=O.[C:29]([C:33]1[CH:38]=[C:37]([CH3:39])[N:36]=[C:35]([NH2:40])[CH:34]=1)([CH3:32])([CH3:31])[CH3:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C>[C:29]([C:33]1[CH:38]=[C:37]([CH3:39])[N:36]=[C:35]([NH:40][C:26](=[O:28])[CH2:25][C:5]2[CH:6]=[CH:7][C:8]([C:10]3[N:14]4[CH:15]=[CH:16][C:17]([C:19]5[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=5)=[CH:18][C:13]4=[N:12][CH:11]=3)=[CH:9][C:4]=2[F:3])[CH:34]=1)([CH3:32])([CH3:31])[CH3:30]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 685394014-(Tert-butyl)-6-methylpyridin-2-amineHCID 68543260[2-Fluoro-4-(7-pyridin-4-yl-imidazo[1,2-a]pyridin-3-yl)-phenyl]-acetic acid dihydrochloride

Product 1

HCID 68543208N-(4-tert-Butyl-6-methyl-pyridin-2-yl)-2-[2-fluoro-4-(7-pyridin-4-yl-imidazo[1,2-a]pyridin-3-yl)-phenyl]-acetamideYield 21.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Combine [2-fluoro-4-(7-pyridin-4-yl-imidazo[1,2-a]pyridin-3-yl)-phenyl]-acetic acid dihydrochloride (0.66 g, 1.57 mmol), 4-tert-butyl-6-methyl-pyridin-2-yl-amine (0.26 g, 1.57 mmol), HATU (0.72 g, 1.57 mmol), diisopropylethylamine (8.12 g, 11.2 mL, 6.28 mmol) in DMF (10 mL) and stir at ambient temperature for 3 hours. Pour the reaction contents onto a pre-washed (with methanol) Varian SCX column (25 g) and wash the column with portions (30 mL) of dichloromethane (2×) and methanol (3×). Elute the product with 2N methanolic ammonia (75 mL) and concentrate the solution to dryness. Chromatograph the crude product on silica using (0-5%) methanol in dichloromethane. Recrystallization from dichloromethane/ether/hexanes provides N-(4-tert-Butyl-6-methyl-pyridin-2-yl)-2-[2-fluoro-4-(7-pyridin-4-yl-imidazo[1,2-a]pyridin-3-yl)-phenyl]-acetamide (0.17 g). MS(ES), m/z 494 (M+1).

Workup

  1. additionPour
  2. customthe reaction contents onto
  3. washa pre-washed (with methanol) Varian SCX column (25 g)
  4. washwash the column with portions (30 mL) of dichloromethane (2×) and methanol (3×)
  5. washElute the product with 2N methanolic ammonia (75 mL)
  6. concentrationconcentrate the solution to dryness
  7. customRecrystallization from dichloromethane/ether/hexanes

Sources & evidence

ORD record
ord-ea59a3f1356e4cb099e995595632da78
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

Loading…