Water → HCID 178419942, compound

HRID 2402165Notes

Reaction equation

HRID 2402165 reaction equation
[N:1]1([C:7]2[S:8][C:9]([C:23]#[N:24])=[C:10]([CH2:12][C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[CH:14]=3)[N:11]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[N-:25]=[N+:26]=[N-:27].[Na+].[Cl-].[NH4+].O>CN(C)C=O.CCOC(C)=O>[CH:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:21]=[CH:22][C:13]=1[CH2:12][C:10]1[N:11]=[C:7]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)[S:8][C:9]=1[C:23]1[NH:27][N:26]=[N:25][N:24]=1

Participants

7

Reactant 4

HCID 962WaterHCID 25517Ammonium ChlorideHCID 33557Sodium AzideHCID 66749241HCID 66749241, compound

Product 1

HCID 178419942HCID 178419942, compoundYield 43.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-(morpholin-4-yl)-4-(2-naphthylmethyl)-1,3-thiazole-5-carbonitrile (213 mg, 0.635 mmol) in N,N-dimethylformamide (3.00 mL) was added sodium azide (61.9 mg, 0.952 mmol) and ammonium chloride (102 mg, 1.90 mmol). The mixture was heated to 100° C. and stirred for 24 hrs. The resulting mixture was cooled to rt and distributed between water and EtOAc. The aqueous layer was extracted with EtOAc (×2). The combined organic layer was washed with 10% LiCl (aq) solution (×2), dried, and concentrated. Purification on HPLC (reverse phase, AA) provided 4-[4-(2-naphthylmethyl)-5-(1H-tetrazol-5-yl)-1,3-thiazol-2-yl]morpholine as a yellow solid (105 mg, 43.7% yield). LCMS: (AA) ES+ 379; 1H NMR (400 MHz, MeOD) δ 7.79-7.61 (m, 4H), 7.43-7.31 (m, 3H), 4.57-4.45 (s, 2H), 3.82-3.68 (t, J=4.9 Hz, 4H), 3.53-3.43 (t, J=4.9 Hz, 4H).

Workup

  1. temperatureThe resulting mixture was cooled to rt
  2. extractionThe aqueous layer was extracted with EtOAc (×2)
  3. washThe combined organic layer was washed with 10% LiCl (aq) solution (×2)
  4. customdried
  5. concentrationconcentrated
  6. customPurification on HPLC (reverse phase, AA)

Sources & evidence

ORD record
ord-64b2c48628f2404f9b2aa55ce3403826
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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