Triphenylphosphine → tert-butyl 4-(2-(6-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)pyridin-2-yloxy)ethyl)piperazine-1-carboxylate

HRID 79347Notes

Reaction equation

HRID 79347 reaction equation
[CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH:12][C:13]([C:15]2[N:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]3=[N:17][CH:16]=2)=[O:14])[N:5]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([OH:31])[N:26]=2)[N:4]=1)[CH3:2].O[CH2:33][CH2:34][N:35]1[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH2:36]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH:12][C:13]([C:15]2[N:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]3=[N:17][CH:16]=2)=[O:14])[N:5]([CH2:24][C:25]2[N:26]=[C:27]([O:31][CH2:33][CH2:34][N:35]3[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:45])([CH3:47])[CH3:46])=[O:42])[CH2:37][CH2:36]3)[CH:28]=[CH:29][CH:30]=2)[N:4]=1)[CH3:2]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 735736Tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylateHCID 178437935HCID 178437935, compound

Product 1

HCID 70815040tert-butyl 4-(2-(6-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)pyridin-2-yloxy)ethyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of N-(3-ethyl-1-((6-hydroxypyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (26 mg, 0.0630 mmol; prepared as in Example 17, Step A) in THF (5 mL) was added tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylate (43.6 mg, 0.189 mmol), triphenylphosphine (41.3 mg, 0.158 mmol) and diethyl azodicarboxylate (62.0 μL, 0.158 mmol). The suspension became a clear solution and was stirred for 16 hours. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel chromatography (DCM/MeOH 10:1) to provide the intermediate tert-butyl 4-(2-(6-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)pyridin-2-yloxy)ethyl)piperazine-1-carboxylate mixed with triphenyl phosphine oxide, to which was added DCM/TFA (2 mL/1 mL). The reaction mixture was stirred for 30 minutes and then concentrated under reduced pressure. Silica gel chromatography (DCM/MeOH/NH4OH 10:1:0.1) provided the desired product (10 mg). MS (ES+APCI) m/z=525 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue was purified by silica gel chromatography (DCM/MeOH 10:1)

Sources & evidence

ORD record
ord-5d0e733587844cedb025523551c79cd0
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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