Triethylamine → 4-[4-(4-Tetrazol-1-yl-phenylcarbamoyl)-thiazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1869517Notes

Reaction equation

HRID 1869517 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[S:15][CH:16]=[C:17]([C:19]([OH:21])=O)[N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[N:51]1([C:56]2[CH:61]=[CH:60][C:59]([NH2:62])=[CH:58][CH:57]=2)[CH:55]=[N:54][N:53]=[N:52]1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]2[S:15][CH:16]=[C:17]([C:19](=[O:21])[NH:62][C:59]3[CH:60]=[CH:61][C:56]([N:51]4[CH:55]=[N:54][N:53]=[N:52]4)=[CH:57][CH:58]=3)[N:18]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5716404-(1H-1,2,3,4-tetrazol-1-yl)anilineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27955312-(1-((Tert-butoxy)carbonyl)piperidin-4-yl)-1,3-thiazole-4-carboxylic acid

Product 1

HCID 579869304-[4-(4-Tetrazol-1-yl-phenylcarbamoyl)-thiazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(4-Carboxy-thiazol-2-yl)-piperidine-1-carboxylic acid tert-butyl ester (1.28 mmol) was dissolved in anhydrous DMF (20 mL). To the solution was added triethylamine (4 eq.) and O-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU) (1.5 eq.). The reaction was allowed to stir at room temperature for 5 minutes before 4-tetrazol-1-yl-phenylamine (1.2 eq.) was added. The reaction was stirred overnight, quenched with water, extracted with ethylacetate, washed with brine, dried over sodium sulfate and filtered. The organic filtrate was concentrated in vacuo and the residual oil was purified by column chromatography (EtOAC/Hex) furnishing the expected product. 1H NMR (CDCl3): δ 9.37 (1H, s), 9.02 (1H, s), 8.14 (1H, s), 7.96 (2H, d), 7.72 (2H, d), 4.23 (2H, m), 3.20 (1H, m), 2.91 (2H, m), 2.14 (2H, m), 1.79 (2H, m), 1.45 (9H, s).

Workup

  1. additionwas added
  2. customquenched with water
  3. extractionextracted with ethylacetate
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationThe organic filtrate was concentrated in vacuo
  8. customthe residual oil was purified by column chromatography (EtOAC/Hex)

Sources & evidence

ORD record
ord-22d43ce141c0410e8f6b093150507e25
Source dataset
uspto-grants-2009_12
Patent number
US07638541B2

Reaction notes

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