Diisopropylethylamine → N-(1-(4-methoxy-3-(2-oxo-2-(4-(1-(pyridin-2-yl)-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-1,2,4-triazol-3-yl)pivalamide

HRID 1157789Notes

Reaction equation

HRID 1157789 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([N:9]2[CH:13]=[N:12][C:11]([NH:14][C:15](=[O:20])[C:16]([CH3:19])([CH3:18])[CH3:17])=[N:10]2)=[C:5]2[NH:21][CH:22]=[C:23]([C:24](=[O:28])[C:25]([OH:27])=O)[C:4]=12.[Cl-].[N:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[N:36]1[C:40]([N:41]2[CH2:46][CH2:45][NH2+:44][CH2:43][CH2:42]2)=[N:39][N:38]=[N:37]1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([N:9]2[CH:13]=[N:12][C:11]([NH:14][C:15](=[O:20])[C:16]([CH3:18])([CH3:19])[CH3:17])=[N:10]2)=[C:5]2[NH:21][CH:22]=[C:23]([C:24](=[O:28])[C:25](=[O:27])[N:44]3[CH2:43][CH2:42][N:41]([C:40]4[N:36]([C:31]5[CH:32]=[CH:33][CH:34]=[CH:35][N:30]=5)[N:37]=[N:38][N:39]=4)[CH2:46][CH2:45]3)[C:4]=12

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 595114512-(4-methoxy-7-(3-pivalamido-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acidHCID 686931734-(1-(pyridin-2-yl)-1H-tetrazol-5-yl)piperazin-1-ium chloride

Product 1

HCID 59511512N-(1-(4-methoxy-3-(2-oxo-2-(4-(1-(pyridin-2-yl)-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-1,2,4-triazol-3-yl)pivalamideYield 43%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(4-methoxy-7-(3-pivalamido-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid (15 mg, 0.039 mmol), 4-(1-(pyridin-2-yl)-1H-tetrazol-5-yl)piperazin-1-ium chloride (11.43 mg, 0.043 mmol), 2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (13.71 mg, 0.043 mmol) and N,N-diisopropyl ethylamine (0.022 ml, 0.124 mmol) in DMF (1 ml) was stirred overnight at room temperature. The reaction mixture was filtered through a silica gel pad and concentrated under reduced pressure. The resulting crude was purified by prep HPLC to give N-(1-(4-methoxy-3-(2-oxo-2-(4-(1-(pyridin-2-yl)-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-1,2,4-triazol-3-yl)pivalamide (10 mg, 43%) as white solid. LCMS: m/e 600.47 (M+H)+, ret time 2.67 min (method 4). 1H NMR (500 MHz, DMSO-D6) δ ppm 1.22 (s, 9H) 3.23-3.29 (m, 2H) 3.39-3.49 (m, 4H) 3.68-3.74 (m, 2H) 3.99 (s, 3H) 7.64 (dd, J=7.63, 4.88 Hz, 1H) 7.85 (d, J=8.24 Hz, 1H) 7.88 (s, 1H) 8.13-8.18 (m, 1H) 8.21 (s, 1H) 8.23 (d, J=3.66 Hz, 1H) 8.64-8.69 (m, 1H) 11.36 (s, 1H) 12.59 (d, J=3.36 Hz, 1H)

Workup

  1. filtrationThe reaction mixture was filtered through a silica gel pad
  2. concentrationconcentrated under reduced pressure
  3. customThe resulting crude was purified by prep HPLC

Sources & evidence

ORD record
ord-b69d2d7e85df4f3290ca66502e383910
Source dataset
uspto-grants-2010_10
Patent number
US07807676B2

Reaction notes

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