Dimethylformamide → 5-iodo-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide

HRID 513035Notes

Reaction equation

HRID 513035 reaction equation
[I:1][C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[CH:9][C:10]([C:11]([OH:13])=O)=[C:4]2[CH:3]=1.[CH3:14][O:15][C:16]1[CH:32]=[CH:31][C:19]([CH2:20][NH:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)=[CH:18][CH:17]=1.CCN=C=NCCCN(C)C.CN(C=O)C>CN(C1C=CN=CC=1)C.O>[I:1][C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[CH:9][C:10]([C:11]([N:21]([CH2:20][C:19]3[CH:18]=[CH:17][C:16]([O:15][CH3:14])=[CH:32][CH:31]=3)[CH2:22][C:23]3[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=3)=[O:13])=[C:4]2[CH:3]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 714952Bis(4-methoxybenzyl)amineHCID 682824725-Iodopyrazolo[1,5-a]pyridine-3-carboxylic acid

Product 1

HCID 682824975-iodo-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolvent

Procedure

A 22 L round bottom flask was charged with 5-iodopyrazolo[1,5-a]pyridine-3-carboxylic acid (I-42) (200 g, 694.3 mmol), bis(4-methoxybenzyl)amine (182.2 g, 708.3 mmol), DMAP (42.4 g, 347.2 mmol), EDCI (146.4 g, 763.8 mmol) and DMF (3500 mL). The suspension was stirred at room temperature over 16 hours and a dark solution was obtained. HPLC showed no (I-42) remaining. 2-MethylTHF (4 L) and water (7 L) were added to the reaction mixture while keeping the batch temperature <25° C. The aqueous layer was separated and extracted with 2-methylTHF (4 L). The combined 2-methylTHF layers were washed with 0.25 N HCl (2×4 L), aqueous saturated NaHCO3 (4 L) and 10% brine (4 L). The 2-methylTHF layer was treated with carbon (20 g) and Na2SO4 (80 g). The solution was passed through a silica gel pad (400 g of silica gel 240-400 mesh) and the pad was washed with 2-MeTHF (3 L). The filtrate was concentrated under vacuum to give 5-iodo-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide (I-43) as a solid. 1H NMR (500 MHz, CDCl3) δ 8.73 (d, 1 H), 8.17 (d, 1H), 7.86 (s, 1H), 7.22 (d, 4 H), 7.14 (dd, 1 H), 6.92 (d, 4 H), 4.68 (s, 4 H), 3.83 (s, 6 H).

Workup

  1. customa dark solution was obtained
  2. customthe batch temperature <25° C
  3. customThe aqueous layer was separated
  4. extractionextracted with 2-methylTHF (4 L)
  5. washThe combined 2-methylTHF layers were washed with 0.25 N HCl (2×4 L), aqueous saturated NaHCO3 (4 L) and 10% brine (4 L)
  6. additionThe 2-methylTHF layer was treated with carbon (20 g) and Na2SO4 (80 g)
  7. washthe pad was washed with 2-MeTHF (3 L)
  8. concentrationThe filtrate was concentrated under vacuum

Sources & evidence

ORD record
ord-88d0ddd0259f4373b816f192505149dd
Source dataset
uspto-grants-2015_08
Patent number
US09102671B2

Reaction notes

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