Isobutyric Acid → HCID 71089610, compound

HRID 710149Notes

Reaction equation

HRID 710149 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.[C:35](O)(=[O:39])[CH:36]([CH3:38])[CH3:37].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.CCOC(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[CH2:29][CH2:30][N:31]([C:35](=[O:39])[CH:36]([CH3:38])[CH3:37])[CH2:32][CH2:33]3)=[N:25][C:24]=2[CH:34]=1

Participants

7

Reactant 4

HCID 6590Isobutyric AcidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 710900805-(2-fluoro-4-(1H-tetrazol-1-yl)phenyl)-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate

Product 1

HCID 71089610HCID 71089610, compoundYield 21.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22728543Water ethylacetateSolvent

Procedure

Tert-butyl 4-{5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate (100 mg, 0.22 mmol) dissolved in DCM (25 ml) and added trifluoroacetic acid (0.4 ml). This mixture stirred at rt for 3 h. After completion of the reaction, DCM removed on rotavapour and residue was co-distilled with ether to obtain 5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate (100 mg). 5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate (100 mg, 0.21 mmol) was dissolved in DMF (3 ml) and added isobutyric acid (202 mg, 0.23 mmol), EDC.HCl (99 mg, 0.52 mmol), HOBt (33 mg, 0.25 mmol) and TEA (0.23 ml, 1.7 mmol). After completion of the reaction, work up (EtOAc/H2O) followed by purification on combiflash using the gradient mixture of EtOAc and Petether (65:35) as eluent afforded the titled compound (20 mg) as a brown solid. M.P.: 190-194° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 9.04 (s, 1H), 7.88 (s, 1H), 7.68 (t, J 8.2, 1H), 7.67-7.59 (m, 2H), 7.52 (td, J 1.6, 8.4, 1H), 4.58 (d, J 12.1, 1H), 4.04 (d, J 13.2, 1H), 3.35-3.22 (m, 2H), 2.96 (t, J 12, 1H), 2.85 (septet, J 6.8, 1H), 2.30-2.18 (m, 2H), 2.05-1.72 (m, 2H), 1.16 (d, J 6.8, 6H).

Workup

  1. customfollowed by purification on combiflash
  2. additionthe gradient mixture of EtOAc and Petether (65:35) as eluent

Sources & evidence

ORD record
ord-fe82f55bc7d841378ba7285f7c64072c
Source dataset
uspto-grants-2015_11
Patent number
US09181214B2

Reaction notes

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