Triethylamine → tert-Butyl 4-(2-(4-(-((6-(1H-tetrazol-1-yl)pyridine-3-yloxy)methyl)-2H-1,2,3-triazol-2-yl)piperidin-1-yl)-2-oxoethyl)piperidine-1-carboxylate

HRID 1928615Notes

Reaction equation

HRID 1928615 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([N:8]2[N:12]=[C:11]([CH2:13][O:14][C:15]3[CH:16]=[CH:17][C:18]([N:21]4[CH:25]=[N:24][N:23]=[N:22]4)=[N:19][CH:20]=3)[CH:10]=[N:9]2)[CH2:4][CH2:3]1.C(N(CC)CC)C.[B-](F)(F)(F)F.CN(C(ON1N=NC2C1=CC=CC=2)=[N+](C)C)C.[C:55]([O:59][C:60]([N:62]1[CH2:67][CH2:66][CH:65]([CH2:68][C:69](O)=[O:70])[CH2:64][CH2:63]1)=[O:61])([CH3:58])([CH3:57])[CH3:56]>CN(C=O)C>[N:21]1([C:18]2[N:19]=[CH:20][C:15]([O:14][CH2:13][C:11]3[CH:10]=[N:9][N:8]([CH:5]4[CH2:4][CH2:3][N:2]([C:69](=[O:70])[CH2:68][CH:65]5[CH2:66][CH2:67][N:62]([C:60]([O:59][C:55]([CH3:57])([CH3:56])[CH3:58])=[O:61])[CH2:63][CH2:64]5)[CH2:7][CH2:6]4)[N:12]=3)=[CH:16][CH:17]=2)[CH:25]=[N:24][N:23]=[N:22]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 1512539[1-(tert-Butoxycarbonyl)piperidin-4-yl]acetic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 687466245-((2-(piperidin-4-yl)-2H-1,2,3-triazol-4-yl)methoxy)-2-(1H-tetrazol-1-yl)pyridine hydrochloride2×

Product 1

HCID 25174586tert-Butyl 4-(2-(4-(-((6-(1H-tetrazol-1-yl)pyridine-3-yloxy)methyl)-2H-1,2,3-triazol-2-yl)piperidin-1-yl)-2-oxoethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 5-((2-(Piperidin-4-yl)-2H-1,2,3-triazol-4-yl)methoxy)-2-(1H-tetrazol-1-yl)pyridine (225 mg, 0.688 mmol) (Intermediate 15) dissolved in DMF (10 mL) was added triethylamine (4 eq.) and o-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU) (2 eq.). The solution was stirred for 5 minutes and 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)acetic acid (1.5 eq.) was added and was stirred at room temperature for 3 h. The reaction was quenched with water and extracted with ethyl acetate. The organic layer was washed with brine, and dried over sodium sulfate. The solution was filtered and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate and hexanes to afford the desired product. 1H NMR (DMSO-d6): δ 10.07 (1H, s), 8.40 (1H, d), 8.00 (1H, d), 7.93 (1H, s), 7.86 (1H, dd), 5.34 (2H, s), 4.78 (1H, m), 4.35 (1H, m), 3.85-3.94 (3H, m), 3.21 (1H, m), 2.64-2.82 (3H, m), 2.27 (2H, d), 2.10 (2H, m), 1.86 (3H, m), 1.60 (2H, d), 1.35 (9H, s), 1.99 (2H, m).

Workup

  1. stirringwas stirred at room temperature for 3 h
  2. customThe reaction was quenched with water
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate and hexanes

Sources & evidence

ORD record
ord-45fbcb143a8d4279808e983e720fb51e
Source dataset
uspto-grants-2012_05
Patent number
US08183381B2

Reaction notes

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