4-Methylmorpholine → HCID 11965207, compound

HRID 1923475Notes

Reaction equation

HRID 1923475 reaction equation
[Na+].[F:2][C:3]([F:22])([F:21])[O:4][C:5]1[CH:10]=[CH:9][C:8]([S:11][C:12]2[CH:20]=[CH:19][C:15]([C:16]([O-:18])=O)=[CH:14][N:13]=2)=[CH:7][CH:6]=1.CN1CCOCC1.[Cl:30]C1N=C(OC)N=C(OC)N=1.[NH:41]1[CH2:45][CH2:44][CH2:43][C@H:42]1[CH2:46][N:47]1[CH2:51][CH2:50][CH2:49][CH2:48]1>ClCCl>[ClH:30].[ClH:30].[N:47]1([CH2:46][C@@H:42]2[CH2:43][CH2:44][CH2:45][N:41]2[C:16]([C:15]2[CH:14]=[N:13][C:12]([S:11][C:8]3[CH:7]=[CH:6][C:5]([O:4][C:3]([F:2])([F:22])[F:21])=[CH:10][CH:9]=3)=[CH:20][CH:19]=2)=[O:18])[CH2:51][CH2:50][CH2:49][CH2:48]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 853152(S)-(+)-1-(2-Pyrrolidinylmethyl)pyrrolidineHCID 67519168HCID 67519168, compound2×

Product 1

HCID 11965207HCID 11965207, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of 6-(4-trifluoromethoxy-phenylsulfanyl)-nicotinic acid sodium salt (54 mg, 0.158 mmol) (see Intermediate 8) and n-methyl morpholine (0.02 mL, 0.158 mmol) in dichloromethane (2.0 mL) in a 0° C. ice bath, add 2-chloro-4,6-dimethoxy-1,3,5-triazine (28 mg, 0.158 mmol). Remove the ice bath and stir for 45 minutes. After this time, add (S)-(+)-1-(2-pyrrolidinylmethyl)pyrrolidine (24 mg, 0.158 mmol) and stir at room temperature for 2 hours. After this time, wash the reaction with saturated aqueous sodium bicarbonate while extracting with 10% isopropanol/dichloromethane. Dry the organic layer with sodium sulfate, filter and concentrate in vacuo. Purify via chromatography eluting with 2M ammonia in methanol and dichloromethane. Dissolve the purified free base in minimal dichloromethane and add 1M HCl in ether in slight excess followed by hexane. Concentrate in vacuo to give the titled compound. MS (m/e): 452.2 (M+1).

Workup

  1. customRemove the ice bath
  2. stirringstir at room temperature for 2 hours
  3. washAfter this time, wash
  4. customthe reaction with saturated aqueous sodium bicarbonate
  5. extractionwhile extracting with 10% isopropanol/dichloromethane
  6. dry with materialDry the organic layer with sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. customPurify via chromatography
  10. washeluting with 2M ammonia in methanol and dichloromethane
  11. dissolutionDissolve the purified free base in minimal dichloromethane
  12. additionadd 1M HCl in ether in slight
  13. concentrationConcentrate in vacuo

Sources & evidence

ORD record
ord-a9b2df6685bb4437b46917687b78e2d0
Source dataset
uspto-grants-2012_05
Patent number
US08178528B2

Reaction notes

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