Diisopropylethylamine → 2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]-5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazole

HRID 710131Notes

Reaction equation

HRID 710131 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]1[CH:14]=[C:13]([N:15]2[CH:19]=[N:18][N:17]=[N:16]2)[CH:12]=[CH:11][C:10]=1[C:20]1[CH:21]=[CH:22][C:23]2[O:27][C:26]([CH:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)=[N:25][C:24]=2[CH:34]=1.CC[N:37](C(C)C)C(C)C.Cl[CH:45]1C[CH2:49][CH:48]([CH2:51][CH3:52])[CH2:47][NH:46]1.CCOC(C)=O.O>CC(O)C>[CH2:51]([C:48]1[CH:49]=[N:37][C:45]([N:31]2[CH2:30][CH2:29][CH:28]([C:26]3[O:27][C:23]4[CH:22]=[CH:21][C:20]([C:10]5[CH:11]=[CH:12][C:13]([N:15]6[CH:19]=[N:18][N:17]=[N:16]6)=[CH:14][C:9]=5[F:8])=[CH:34][C:24]=4[N:25]=3)[CH2:33][CH2:32]2)=[N:46][CH:47]=1)[CH3:52]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 22728543Water ethylacetateHCID 710900805-(2-fluoro-4-(1H-tetrazol-1-yl)phenyl)-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetateHCID 866769522-Chloro-5-ethyl piperidine

Product 1

HCID 711141922-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]-5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazole

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

Tert-butyl 4-{5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate (120 mg, 0.26 mmol) dissolved in DCM (15 ml) and added Trifluoroacetic acid (0.5 ml). This mixture was stirred at rt for 2 h. DCM removed from the reaction mixture to obtain 5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate (150 mg). 5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate (70 mg, 0.15 mmol) was dissolved in IPA (10 ml), added DiPEA (0.25 ml, 1.2 mmol) and stirred at rt for 30 mins 2-Chloro-5-ethyl piperidine was added to the above reaction mixture and heated the reaction mixture to 90° C. for overnight. After completion of the reaction, work-up (EtOAc/H2O) followed by purification on combiflash using the gradient mixture of ethyl acetate and petether (1:1) as eluent afforded the titled compound (20 mg) as an off-white solid. M.P.: 188-192° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 9.03 (s, 1H), 8.20 (s, 2H), 7.88 (s, 1H), 7.68 (t, J 8.2, 1H), 7.65-7.58 (m, 3H), 7.54-7.49 ((m, 1H), 4.80-4.70 (m, 2H), 3.33-3.23 (m, 1H), 3.22 (t, J 14, 2H), 2.48 (q, J 7.6, 2H), 2.30-2.22 (m, 2H), 2.07-1.95 (m, 2H), 1.20 (t, J 7.6, 3H).

Workup

  1. additionwas added to the above reaction mixture
  2. customAfter completion of the reaction
  3. customfollowed by purification on combiflash
  4. additionthe gradient mixture of ethyl acetate and petether (1:1) as eluent

Sources & evidence

ORD record
ord-94506b4b40d04ba183ae7a8eddc0fe30
Source dataset
uspto-grants-2015_11
Patent number
US09181214B2

Reaction notes

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