Diisopropylethylamine → 4-(3-fluoro-azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid (2-morpholin-4-yl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-amide

HRID 1802215Notes

Reaction equation

HRID 1802215 reaction equation
[CH3:1][N:2]1[C:6]([C:7](=[O:24])[NH:8][C:9]2[CH:14]=[CH:13][N:12]3[N:15]=[C:16]([N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)[N:17]=[C:11]3[CH:10]=2)=[C:5]([C:25](O)=[O:26])[CH:4]=[N:3]1.Cl.[F:29][CH:30]1[CH2:33][NH:32][CH2:31]1.C(N(C(C)C)C(C)C)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>O1CCCC1>[N:18]1([C:16]2[N:17]=[C:11]3[CH:10]=[C:9]([NH:8][C:7]([C:6]4[N:2]([CH3:1])[N:3]=[CH:4][C:5]=4[C:25]([N:32]4[CH2:33][CH:30]([F:29])[CH2:31]4)=[O:26])=[O:24])[CH:14]=[CH:13][N:12]3[N:15]=2)[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 101250543-fluoroazetidine HydrochlorideHCID 677757071-methyl-5-(2-morpholino-[1,2,4]triazolo[1,5-a]pyridin-7-ylcarbamoyl)-1H-pyrazole-4-carboxylic acid

Product 1

HCID 573779564-(3-fluoro-azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid (2-morpholin-4-yl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-amideYield 39.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-methyl-5-(2-morpholin-4-yl-[1,2,4]triazolo[1,5-a]pyridin-7-ylcarbamoyl)-1H-pyrazole-4-carboxylic acid (150 mg, 0.404 mmole), 3-fluoroazetidine hydrochloride (135 mg, 1.21 mmole), N-ethyldiisopropylamine (353 ul, 2.02 mmole) and 1-propanephosphonic acid cyclic anhydride (50% in ethyl acetate, 606 ul, 1.01 mmole) in tetrahydrofurane (7 ml) is stirred for 22 h at room temperature. The solvent is removed under reduced pressure and the residue (994 mg) is triturated for 2 hrs with sat. aqueous sodium bicarbonate solution (30 ml). The solid is collected by filtration, washed with water and dried affording 4-(3-fluoro-azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid (2-morpholin-4-yl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-amide (68 mg, 39.3%) as an off-white solid. mp.: 247-250° C. MS: m/z=425.1 (M+H+)

Workup

  1. customThe solvent is removed under reduced pressure
  2. customthe residue (994 mg) is triturated for 2 hrs with sat. aqueous sodium bicarbonate solution (30 ml)
  3. filtrationThe solid is collected by filtration
  4. washwashed with water
  5. customdried

Sources & evidence

ORD record
ord-474582b4323d4fd69e2366a6dcdc3c9d
Source dataset
uspto-grants-2013_01
Patent number
US08349824B2

Reaction notes

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