Tetrahydrofuran → 1-(2-{3-[2-(8-Aza-bicyclo[3.2.1]oct-8-yl)-ethoxy]-phenyl}-5-tert-butyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt

HRID 630987

Reaction equation

HRID 630987 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C@@H:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C@H:17]([O:24][C:25]3[CH:26]=[CH:27][C:28]4[N:29]([C:31]([N:34]5[CH2:39][CH2:38][CH2:37][CH2:36][C@@H:35]5[CH3:40])=[N:32][N:33]=4)[CH:30]=3)[CH2:16][CH2:15]2)=[O:12])[N:7]([C:41]2[CH:42]=[C:43]([CH:52]=[CH:53][CH:54]=2)[O:44][CH2:45][CH2:46][O:47]S(C)(=O)=O)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH:55]12[NH:62][CH:59]([CH2:60][CH2:61]1)[CH2:58][CH2:57][CH2:56]2.C1C[O:66]CC1>>[CH:46]([OH:47])=[O:66].[CH:59]12[N:62]([CH2:46][CH2:45][O:44][C:43]3[CH:42]=[C:41]([N:7]4[C:8]([NH:10][C:11]([NH:13][C@@H:14]5[C:23]6[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=6)[C@H:17]([O:24][C:25]6[CH:26]=[CH:27][C:28]7[N:29]([C:31]([N:34]8[CH2:39][CH2:38][CH2:37][CH2:36][C@@H:35]8[CH3:40])=[N:32][N:33]=7)[CH:30]=6)[CH2:16][CH2:15]5)=[O:12])=[CH:9][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[N:6]4)[CH:54]=[CH:53][CH:52]=3)[CH:55]([CH2:61][CH2:60]1)[CH2:56][CH2:57][CH2:58]2

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 1360978-Azabicyclo(3.2.1)octaneHCID 86687292Methanesulfonic acid 2-{3-[3-tert-butyl-5-(3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-pyrazol-1-yl]-phenoxy}-ethyl ester

Product 1

HCID 866873081-(2-{3-[2-(8-Aza-bicyclo[3.2.1]oct-8-yl)-ethoxy]-phenyl}-5-tert-butyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate saltYield 62%

Procedure

A solution of Intermediate 154a (50.5 mg, 66 μmol) and 8-aza-bicyclo[3.2.1]octane (38 mg, 0.34 mmol) in THF (1 mL) was heated at 60° C. overnight in a sealed vessel. The reaction mixture was concentrated in vacuo and the residue purified by MDAP (Method 7) to give the title compound as a white solid (32 mg, 62%). LCMS (Method 5): Rt 3.84 min, m/z 772 [MH+]. 1H NMR (400 MHz, d6-DMSO): 0.91 (3H, d, J=6.4 Hz), 1.21-1.36 (11H, m), 1.37-1.54 (4H, m), 1.58-1.72 (4H, m), 1.74-2.18 (8H, m), 2.72 (2H, d, J=6.4 Hz), 2.86-2.95 (1H, m), 3.11-3.20 (1H, m), 3.22-3.36 (5H, m), 4.09 (2H, t, J=6.1 Hz), 4.77-4.86 (1H, m), 5.52 (1H, t, J=4.1 Hz), 6.33 (1H, s), 6.94-6.99 (1H, m), 7.04-7.11 (2H, m), 7.14 (1H, d, J=8.6 Hz), 7.18 (1H, dd, J=10.2 Hz, 2.1 Hz), 7.24-7.42 (5H, m), 7.64 (1H, d, J=10.2 Hz), 7.69 (1H, d, J=2.0 Hz), 8.17 (1H, s), 8.19 (1.6H, s).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue purified by MDAP (Method 7)

Sources & evidence

ORD record
ord-d8e2a4e206f64dcdb664752217076088
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Linked notes

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