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Diisopropylethylamine → 1-{5-tert-Butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-{4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-cyclohexyl}-urea

HRID 2200047
Notes
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Reaction equation

HRID 2200047 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][C@@H:32](C)[N:31]1[C:37]1[N:41]2[CH:42]=[C:43]([O:46][CH:47]3[CH2:52][CH2:51][CH:50]([NH2:53])[CH2:49][CH2:48]3)[CH:44]=[CH:45][C:40]2=[N:39][N:38]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[C:12]([C:10]1[CH:11]=[C:7]([NH:6][C:5]([NH:53][CH:50]2[CH2:51][CH2:52][CH:47]([O:46][C:43]3[CH:44]=[CH:45][C:40]4[N:41]([C:37]([N:31]5[CH2:32][CH2:33][CH2:34][CH2:35][C@@H:30]5[CH3:29])=[N:38][N:39]=4)[CH:42]=3)[CH2:48][CH2:49]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)([CH3:14])([CH3:13])[CH3:15]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

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 1177290354-[3-((2S,6R)-2,6-Dimethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-cyclohexylamine

Product 1

HCID 1177291641-{5-tert-Butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-{4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-cyclohexyl}-urea
Yield 82%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of {5-tert-butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-carbamic acid 2,2,2-trichloro-ethyl ester (WO 2007/063868, which is incorporated herein by reference in its entirety, 287.6 mg, 0.638 mmol), Intermediate 18a (140 mg, 0.425 mmol) and DIPEA (223 μL, 1.28 mmol) in dioxane (10 mL) was stirred at 60° C. for 18 h. The volatiles were concentrated in vacuo and the resultant residue was purified by FCC, using 0-10% [2M NH3 in MeOH] in DCM, to afford the title compound (222 mg, 82%). LCMS (Method 3): Rt 3.35 min, m/z 631 [MH+].

Workup

  1. concentrationThe volatiles were concentrated in vacuo
  2. customthe resultant residue was purified by FCC

Sources & evidence

ORD record
ord-a9f94e6e741c4c4091970e853863f2a8
Source dataset
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09359354B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes