Triethylamine → 3-(4-{4-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperazine-1-carbonyl)-adamantane-1-carboxylic acid

HRID 1691953Notes

Reaction equation

HRID 1691953 reaction equation
Cl.[N:2]1([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]3[N:18]=[C:19]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[O:20][C:21]=3[C:22]([F:25])([F:24])[F:23])=[O:16])=[CH:10][CH:9]=2)[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[C:32]12([C:45](O)=[O:46])[CH2:41][CH:36]3[CH2:37][CH:38]([CH2:40][C:34]([C:42]([OH:44])=[O:43])([CH2:35]3)[CH2:33]1)[CH2:39]2.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C.C(OCC)(=O)C>[C:26]1([C:19]2[O:20][C:21]([C:22]([F:23])([F:25])[F:24])=[C:17]([C:15]([NH:14][C:11]3[CH:12]=[CH:13][C:8]([N:2]4[CH2:7][CH2:6][N:5]([C:45]([C:32]56[CH2:41][CH:36]7[CH2:37][CH:38]([CH2:40][C:34]([C:42]([OH:44])=[O:43])([CH2:35]7)[CH2:33]5)[CH2:39]6)=[O:46])[CH2:4][CH2:3]4)=[CH:9][CH:10]=3)=[O:16])[N:18]=2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 643391,3-Adamantanedicarboxylic acidHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 667383362-Phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (4-piperazin-1-yl-phenyl)-amide hydrochloride

Product 1

HCID 251225553-(4-{4-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperazine-1-carbonyl)-adamantane-1-carboxylic acidYield 13.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-Phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (4-piperazin-1-yl-phenyl)-amide, hydrochloride (51.5 mg, 0.113 mmol), adamantane-1,3-dicarboxylic acid (51 mg, 0.227 mmol), and triethylamine (48 uL, 0.341 mmol) were dissolved in 1 mL of DMF. To this solution was added BOP (52 mg, 0.122 mmol) in one portion. The mixture was stirred at room temperature overnight. 4-N,N-dimethylamino-pyridine (5 mg) was added and the reaction was stirred for an additional 72 hours and then diluted with 30 ml ethyl acetate. The organic phase was washed with saturated ammonium chloride (1×5 mL), 2.5% KHSO4 (3×5 mL), water (2×5 mL) and saturated sodium chloride. The organic layer was dried over MgSO4, filtered, passed through a plug of silica gel and evaporated to dryness under vacuum to a light brown solid. The residue was purified by flash chromatography to yield 3-(4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperazine-1-carbonyl)-adamantane-1-carboxylic acid as light yellow crystals (9.4 mg, 13%). ES-MS calcd for C33H33F3N4O5 (m/e) 622.65, obsd 623 (M+H).

Workup

  1. stirringthe reaction was stirred for an additional 72 hours
  2. washThe organic phase was washed with saturated ammonium chloride (1×5 mL), 2.5% KHSO4 (3×5 mL), water (2×5 mL) and saturated sodium chloride
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. customevaporated to dryness under vacuum to a light brown solid
  6. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-e8984dfdd0b5448a9d2dcad28e3478eb
Source dataset
uspto-grants-2012_04
Patent number
US08153644B2

Reaction notes

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