Ammonia → Tert-butyl 4-(4-(2-(o-toluidino)-4-carbamoyloxazol-5-yl)phenyl)piperazine-1-carboxylate

HRID 389763Notes

Reaction equation

HRID 389763 reaction equation
[C:1]1([CH3:35])[C:2]([NH:7][C:8]2[O:9][C:10]([C:16]3[CH:21]=[CH:20][C:19]([N:22]4[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]4)=[CH:18][CH:17]=3)=[C:11]([C:13](O)=[O:14])[N:12]=2)=[CH:3][CH:4]=[CH:5][CH:6]=1.O.OC1C2N=N[NH:43]C=2C=CC=1.Cl.CN(C)CCCN=C=NCC.N.O1CCOCC1>C(Cl)Cl.CN(C=O)C>[C:1]1([CH3:35])[C:2]([NH:7][C:8]2[O:9][C:10]([C:16]3[CH:17]=[CH:18][C:19]([N:22]4[CH2:23][CH2:24][N:25]([C:28]([O:30][C:31]([CH3:32])([CH3:33])[CH3:34])=[O:29])[CH2:26][CH2:27]4)=[CH:20][CH:21]=3)=[C:11]([C:13](=[O:14])[NH2:43])[N:12]=2)=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

8

Reactant 5

HCID 222Ammonia3×HCID 312751,4-Dioxane3×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride3×HCID 595875892-(o-Toluidino)-5-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)oxazole-4-carboxylic acidHCID 178526939HCID 178526939, compound3×

Product 1

HCID 59587624Tert-butyl 4-(4-(2-(o-toluidino)-4-carbamoyloxazol-5-yl)phenyl)piperazine-1-carboxylateYield 32%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(o-toluidino)-5-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)oxazole-4-carboxylic acid (0.038, 0.08 mmol) in DCM (0.8 ml) and DMF (0.6 ml) was added hydroxybenzotriazole monohydrate (0.016 g, 0.10 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.024 g, 0.13 mmol) and 0.5M ammonia in dioxane (0.8 ml, 0.4 mmol) and the resultant mixture stirred overnight at room temperature. A further portion each of hydroxybenzotriazole monohydrate (0.016 g, 0.10 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.024 g, 0.13 mmol) and 0.5M ammonia in dioxane (0.8 ml, 0.4 mmol) was added and the resultant mixture stirred for 5 hours at room temperature, followed by the addition of hydroxybenzotriazole monohydrate (0.008 g, 0.05 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.012 g, 0.065 mmol) and 0.5M ammonia in dioxane (0.4 ml, 0.2 mmol) and the reaction mixture was stirred overnight. The solvent was then removed in vacuo and the residue purified by preparative HPLC to afford tert-butyl 4-(4-(2-(o-toluidino)-4-carbamoyloxazol-5-yl)phenyl)piperazine-1-carboxylate (0.012 g, 0.025 mmol, 32%). LCMS (2) Rt: 3.41 min; m/z (ES+) 478.

Workup

  1. customThe solvent was then removed in vacuo
  2. customthe residue purified by preparative HPLC

Sources & evidence

ORD record
ord-1bb8b6b4e9a54b16b338fb95cd60cd78
Source dataset
uspto-grants-2013_02
Patent number
US08378095B2

Reaction notes

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