Hydrochloric Acid → N-(4'-Amino-5'-methylspiro[chroman-4,2'-imidazole]-6-yl)-5-chloropicolinamide

HRID 539320

Reaction equation

HRID 539320 reaction equation
Cl.CN(C)CCCN=C=NCC.[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]([OH:22])=O)=[N:18][CH:19]=1.[CH3:23][C:24]1[C:25]([NH2:39])=[N:26][C:27]2([C:37]3[C:32](=[CH:33][CH:34]=[C:35]([NH2:38])[CH:36]=3)[O:31][CH2:30][CH2:29]2)[N:28]=1.Cl>C(Cl)Cl.CN(C=O)C>[NH2:39][C:25]1[C:24]([CH3:23])=[N:28][C:27]2([C:37]3[C:32](=[CH:33][CH:34]=[C:35]([NH:38][C:20](=[O:22])[C:17]4[CH:16]=[CH:15][C:14]([Cl:13])=[CH:19][N:18]=4)[CH:36]=3)[O:31][CH2:30][CH2:29]2)[N:26]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27628725-Chloro-2-picolinic acidHCID 679794075'-Methylspiro[chromane-4,2'-imidazole]-4',6-diamine2×

Product 1

HCID 57385111N-(4'-Amino-5'-methylspiro[chroman-4,2'-imidazole]-6-yl)-5-chloropicolinamideYield 31.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (58 mg, 0.30 mmol) was added to a suspension of 5-chloropyridine-2-carboxylic acid (37 mg, 0.23 mmol) in DCM (1.5 mL). The obtained solution was stirred for 10 min and added dropwise over 2 min to an ice-cooled solution of 5′-methylspiro[chroman-4,2′-imidazole]-4′,6-diamine (Intermediate 30, 54 mg, 0.23 mmol) and 2 M HCl (0.117 mL, 0.23 mmol) in DMF (1.5 mL). The mixture was stirred at 0° C. for 5 min. Volatiles were removed in vacuo, and the residue was purified by preparative chromatography. Fractions containing the product were combined, and the organic solvent was removed in vacuo. The aqueous residue was alkalized with (sat) NaHCO3 and then extracted twice with EtOAc. The combined organic phases were dried (Na2SO4) and evaporated to give a product which was purified by flash chromatography (4 g, gradient elution (EtOAc/MeOH/conc. NH3) in heptane) affording the title compound (27 mg, 31% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.92 (br. s., 2 H), 2.23 (s, 3 H), 4.23-4.54 (m, 2 H), 6.56 (br. s., 2 H), 6.80 (d, 1 H), 7.05 (br. s., 1 H), 7.54-7.72 (m, 1 H), 8.04-8.12 (m, 1 H), 8.13-8.23 (m, 1 H), 8.72 (br. s., 1 H), 10.41 (s, 1 H); HPLC, MS (APCI+) m/z 370 [M+H]+.

Workup

  1. stirringThe mixture was stirred at 0° C. for 5 min
  2. customVolatiles were removed in vacuo
  3. customthe residue was purified by preparative chromatography
  4. additionFractions containing the product
  5. customthe organic solvent was removed in vacuo
  6. extractionextracted twice with EtOAc
  7. dry with materialThe combined organic phases were dried (Na2SO4)
  8. customevaporated
  9. customto give a product which
  10. customwas purified by flash chromatography (4 g, gradient elution (EtOAc/MeOH/conc. NH3) in heptane)

Sources & evidence

ORD record
ord-0b4ccc2351f343ffa0a29b80e6bc54ed
Source dataset
uspto-grants-2014_10
Patent number
US08865911B2

Linked notes

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