Water → HCID 71280509, compound

HRID 1497873Notes

Reaction equation

HRID 1497873 reaction equation
[CH:1]([Si:4]([CH:22]([CH3:24])[CH3:23])([CH:19]([CH3:21])[CH3:20])[O:5][CH2:6][C:7]1[CH:8]=[CH:9][C:10]2[N:11]([C:13]([C:16](O)=[O:17])=[CH:14][N:15]=2)[CH:12]=1)([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O.[F:31][C:32]1([F:49])[CH2:35][CH:34]([C:36]2[O:40][N:39]=[C:38]([C:41]3[CH:42]=[CH:43][C:44]([CH3:48])=[C:45]([CH:47]=3)[NH2:46])[N:37]=2)[CH2:33]1.O>ClCCl.CN(C=O)C.N1C=CC=CC=1>[F:49][C:32]1([F:31])[CH2:33][CH:34]([C:36]2[O:40][N:39]=[C:38]([C:41]3[CH:42]=[CH:43][C:44]([CH3:48])=[C:45]([NH:46][C:16]([C:13]4[N:11]5[CH:12]=[C:7]([CH2:6][O:5][Si:4]([CH:1]([CH3:2])[CH3:3])([CH:22]([CH3:23])[CH3:24])[CH:19]([CH3:21])[CH3:20])[CH:8]=[CH:9][C:10]5=[N:15][CH:14]=4)=[O:17])[CH:47]=3)[N:37]=2)[CH2:35]1

Participants

8

Reactant 4

HCID 962WaterHCID 65578Oxalyl chlorideHCID 712813276-(((Triisopropylsilyl)oxy)methyl)imidazo[1,2-a]pyridine-3-carboxylic acidHCID 86677525HCID 86677525, compound

Product 1

HCID 71280509HCID 71280509, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirring suspension of 6-(((triisopropylsilyl)oxy)methyl)imidazo[1,2-a]pyridine-3-carboxylic acid (61) (260 mg, 0.74 mmol) in anhydrous dichloromethane (5 mL) at room temperature oxalyl chloride was added dropwise (0.19 mL, 2.22 mmol). Then, one drop of anhydrous DMF was added and the reaction mixture was stirred at room temperature for 15 minutes. The solvent was concentrated and the crude solid was added to a stirring solution of 5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylaniline (37) (180 mg, 0.74 mmol) in anhydrous pyridine (5 mL) at room temperature. The reaction was stirred for 20 minutes and the solvent was removed to afford residue. To the above residue was added water (20 mL) and sonicated to give precipitate. Then the precipitate was filtered, dried in air and purified by silica chromatography to afford N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(((triisopropylsilyl)oxy)methyl)imidazo[1,2-a]pyridine-3-carboxamide (64). MS m/z 596.3 (M+1)+.

Workup

  1. additionwas added dropwise (0.19 mL, 2.22 mmol)
  2. concentrationThe solvent was concentrated
  3. stirringThe reaction was stirred for 20 minutes
  4. customthe solvent was removed
  5. customto afford residue
  6. customsonicated
  7. customto give precipitate
  8. filtrationThen the precipitate was filtered
  9. customdried in air
  10. custompurified by silica chromatography

Sources & evidence

ORD record
ord-67c0ad45c974428fab6f5338e24146bf
Source dataset
uspto-grants-2015_12
Patent number
US09199981B2

Reaction notes

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