Water → HCID 178510280, compound

HRID 2401902Notes

Reaction equation

HRID 2401902 reaction equation
[N-:1]=[N+:2]=[N-:3].[Na+].[Si](Cl)(Cl)(Cl)Cl.[C:10]([C:12]1[C:13]([CH2:26][C:27]2[CH:36]=[CH:35][C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH:28]=2)=[C:14]([C:23]([NH2:25])=O)[S:15][C:16]=1[N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)#[N:11].O>C(#N)C.CCOC(C)=O>[N:17]1([C:16]2[S:15][C:14]([C:23]3[NH:25][N:3]=[N:2][N:1]=3)=[C:13]([CH2:26][C:27]3[CH:36]=[CH:35][C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH:28]=3)[C:12]=2[C:10]#[N:11])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1

Participants

7

Reactant 4

HCID 962WaterHCID 24816Silicon tetrachlorideHCID 33557Sodium AzideHCID 66748114HCID 66748114, compound

Product 1

HCID 178510280HCID 178510280, compoundYield 20.9%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of sodium azide (153 mg, 2.35 mmol) in acetonitrile (2.50 mL) in a 20 mL microwave tube was added silicon(IV) chloride (89.9 uL, 0.783 mmol). The mixture was stirred at rt under an atmosphere of Nitrogen for 20 min, then 4-cyano-5-(morpholin-4-yl)-3-(2-naphthylmethyl)thiophene-2-carboxamide (197 mg, 0.522 mmol) was added. The tube was sealed and the reaction was heated to 90° C. for 12 hrs. The mixture was cooled and distributed between water and EtOAc. The aqueous layer was extracted with EtOAc (×2). The combined organic layer was washed with brine, dried, and concentrated to provide a purple syrup. Purification on HPLC (reverse phase, AA) provided 2-(morpholin-4-yl)-4-(2-naphthylmethyl)-5-(1H-tetrazol-5-yl)thiophene-3-carbonitrile as a yellow solid (44 mg, 20.9% yield). LCMS: (AA) ES+ 403; 1H NMR (400 MHz, MeOD) δ 7.78-7.73 (m, 1H), 7.73-7.67 (d, J=7.8 Hz, 2H), 7.67-7.61 (s, 1H), 7.42-7.36 (m, 2H), 7.36-7.30 (m, 1H), 4.63-4.57 (s, 2H), 3.85-3.76 (t, J=4.9 Hz, 4H), 3.57-3.48 (t, J=4.8 Hz, 4H).

Workup

  1. customThe tube was sealed
  2. temperaturethe reaction was heated to 90° C. for 12 hrs
  3. temperatureThe mixture was cooled
  4. extractionThe aqueous layer was extracted with EtOAc (×2)
  5. washThe combined organic layer was washed with brine
  6. customdried
  7. concentrationconcentrated
  8. customto provide a purple syrup
  9. customPurification on HPLC (reverse phase, AA)

Sources & evidence

ORD record
ord-7b28194576994f81bd124a978a639fc2
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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