Dimethylacetamide → HCID 58072102, compound

HRID 870542Notes

Reaction equation

HRID 870542 reaction equation
N[CH2:2][C@H:3]1[CH2:7][NH:6][C:5](=[O:8])[CH2:4]1.Cl[C:10]1[N:19]=[C:18]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)=[C:22]([O:33][CH3:34])[CH:21]=2)[CH:17]=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2.CC(N(C)C)=[O:37]>>[CH3:34][O:33][C:22]1[CH:21]=[C:20]([C:18]2[CH:17]=[C:16]3[C:11]([CH:12]=[CH:13][CH:14]=[N:15]3)=[C:10]([O:37][CH2:2][C@H:3]3[CH2:7][NH:6][C:5](=[O:8])[CH2:4]3)[N:19]=2)[CH:25]=[CH:24][C:23]=1[O:26][CH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1

Participants

4

Reactant 3

HCID 31374Dimethylacetamide2×HCID 51606335HCID 51606335, compoundHCID 58072087HCID 58072087, compound

Product 1

HCID 58072102HCID 58072102, compound

Procedure

91 mg (R)-4-Hydroxymethyl-pyrrolidine-2-one (2.2) was placed in 1 mL of dimethylacetamide at ambient temperature under nitrogen. The reaction was stirred for 10 min before 210 mg 5-chloro-7-[3-methoxy-4-(tetrahydro-pyran-4-yloxy)-phenyl]-[1,6]naphthyridine (6.36) as a solution in 1.5 mL dimethylacetamide was introduced. The reaction was stirred overnight at ambient temperature and then heated to 70° C. where it was maintained for 2 h. After this time the mixture was cooled to ambient temperature and it was partitioned between water and ethyl acetate. The aqueous layer was separated and it was extracted with additional ethyl acetate (×2). The combined organic fractions were dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. Purification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 92:8) gave the title compound.

Workup

  1. additionwas introduced
  2. temperatureheated to 70° C. where it
  3. temperaturewas maintained for 2 h
  4. temperatureAfter this time the mixture was cooled to ambient temperature
  5. customit was partitioned between water and ethyl acetate
  6. customThe aqueous layer was separated
  7. extractionit was extracted with additional ethyl acetate (×2)
  8. dry with materialThe combined organic fractions were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customPurification by silica gel chromatography (ethyl acetate/methanol: 100:0 to 92:8)

Sources & evidence

ORD record
ord-6f5173e75e1f4bdd99402542bccf6f70
Source dataset
uspto-grants-2015_03
Patent number
US08969568B2

Reaction notes

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