Diisopropylethylamine → 1-{5-tert-Butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-[(1S,4S)-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

HRID 631012Notes

Reaction equation

HRID 631012 reaction equation
ClC(Cl)(Cl)CO[C:5](=[O:26])[NH:6][C:7]1[N:8]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH2:23][CH2:24][OH:25])[CH:17]=2)[N:9]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:11]=1.[CH3:29][C@H:30]1[CH2:35][CH2:34][CH2:33][CH2:32][N:31]1[C:36]1[N:40]2[CH:41]=[C:42]([O:45][C@@H:46]3[C:55]4[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=4)[C@@H:49]([NH2:56])[CH2:48][CH2:47]3)[CH:43]=[CH:44][C:39]2=[N:38][N:37]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[C:12]([C:10]1[CH:11]=[C:7]([NH:6][C:5]([NH:56][C@@H:49]2[C:50]3[C:55](=[CH:54][CH:53]=[CH:52][CH:51]=3)[C@@H:46]([O:45][C:42]3[CH:43]=[CH:44][C:39]4[N:40]([C:36]([N:31]5[CH2:32][CH2:33][CH2:34][CH2:35][C@@H:30]5[CH3:29])=[N:37][N:38]=4)[CH:41]=3)[CH2:47][CH2:48]2)=[O:26])[N:8]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH2:23][CH2:24][OH:25])[CH:17]=2)[N:9]=1)([CH3:15])([CH3:14])[CH3:13]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 59151941{5-tert-Butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-carbamic acid 2,2,2-trichloro-ethyl esterHCID 86687322(1S,4S)-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-ylamine

Product 1

HCID 896241921-{5-tert-Butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-[(1S,4S)-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]-ureaYield 61.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of Intermediate 148e (313 mg, 0.7 mmol), Intermediate 186b (262 mg, 0.7 mmol) and DIPEA (182 μL, 1.05 mmol) in dioxane (4 mL) was heated at 70° C. for 20 h. The reaction mixture was cooled to RT and eluted directly on SCX-2 using MeOH and 2M NH3 in MeOH. The basic fractions were evaporated under reduced pressure. The residue was purified by FCC, using 0-10% [2M NH3 in MeOH] in DCM, to afford the title compound as a yellow glass (293 mg). LCMS (Method 3): Rt 3.63 min, m/z 679 [MH+].

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. washeluted directly on SCX-2 using MeOH and 2M NH3 in MeOH
  3. customThe basic fractions were evaporated under reduced pressure
  4. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-6ca51d0308844e538069e29cf97535e0
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

Loading…