Hydrochloric Acid → HCID 11629007, compound

HRID 2378121Notes

Reaction equation

HRID 2378121 reaction equation
[N-:1]=[N+:2]=[N-:3].[Na+].Cl.C(N(CC)CC)C.[C:13]([CH2:15][CH2:16][O:17][C:18]([N:20]1[C:29]2[C:24](=[N:25][C:26]([C:30]([F:33])([F:32])[F:31])=[CH:27][CH:28]=2)[C@@H:23]([N:34]([CH2:41][C:42]2[CH:47]=[C:46]([C:48]([F:51])([F:50])[F:49])[CH:45]=[C:44]([C:52]([F:55])([F:54])[F:53])[CH:43]=2)[C:35]2[N:36]=[N:37][N:38]([CH3:40])[N:39]=2)[CH2:22][C@H:21]1[CH2:56][CH3:57])=[O:19])#[N:14].Cl>C1(C)C=CC=CC=1>[N:1]1[NH:2][N:3]=[N:14][C:13]=1[CH2:15][CH2:16][O:17][C:18]([N:20]1[C:29]2[C:24](=[N:25][C:26]([C:30]([F:33])([F:32])[F:31])=[CH:27][CH:28]=2)[C@@H:23]([N:34]([CH2:41][C:42]2[CH:43]=[C:44]([C:52]([F:55])([F:54])[F:53])[CH:45]=[C:46]([C:48]([F:51])([F:50])[F:49])[CH:47]=2)[C:35]2[N:36]=[N:37][N:38]([CH3:40])[N:39]=2)[CH2:22][C@H:21]1[CH2:56][CH3:57])=[O:19]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11130Triethylamine hydrochloride3×HCID 33557Sodium Azide3×HCID 11714395HCID 11714395, compound

Product 1

HCID 11629007HCID 11629007, compoundYield 66.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Add sodium azide (16 mg, 0.24 mmol) and triethylamine hydrochloride (33 mg, 0.24 mmol) to a solution of (2R,4S)-4-[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid 2-cyano-ethyl ester (77 mg, 0.12 mmol) in toluene (2.4 mL). Stir the mixture at 80° C. for 1.5 h and at 100° C. overnight. Add more sodium azide (24 mg, 0.36 mmol) and triethylamine hydrochloride (50 mg, 0.36 mmol) and stir the mixture for 8 h at 100° C. Add more sodium azide (24 mg, 0.36 mmol) and triethylamine hydrochloride (50 mg, 0.36 mmol) and stir the mixture for 6 h at 100° C. Cool down to room temperature. Add 1 M HCl and extract the aqueous phase with dichloromethane. Wash the organic layers with water and brine, then dry over Na2SO4, filter, and concentrate. Purify the crude material by silica gel chromatography (elution with dichloromethane/methanol) to afford the title compound (55 mg, 66%). MS (ES+): 694 (M+H).

Workup

  1. customat 100° C.
  2. customovernight
  3. stirringstir the mixture for 8 h at 100° C
  4. stirringstir the mixture for 6 h at 100° C
  5. temperatureCool down to room temperature
  6. extractionextract the aqueous phase with dichloromethane
  7. washWash the organic layers with water and brine
  8. dry with materialdry over Na2SO4
  9. filtrationfilter
  10. concentrationconcentrate
  11. customPurify the crude material
  12. washby silica gel chromatography (elution with dichloromethane/methanol)

Sources & evidence

ORD record
ord-a186beed88e94ad7ba98b54dc7a72838
Source dataset
uspto-grants-2008_12
Patent number
US07470705B2

Reaction notes

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