Triethylamine → N-[3-tert-butyl-1-(4-{2-[(3S)-3-hydroxypyrrolidin-1-yl]-2-oxoethyl}phenyl)-1H-pyrazol-5-yl]-N'-[4-(pyridin-4-yloxy)phenyl]urea

HRID 1174886Notes

Reaction equation

HRID 1174886 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)=[CH:16][CH:15]=2)=[O:12])[N:7]([C:27]2[CH:32]=[CH:31][C:30]([CH2:33][C:34]([OH:36])=O)=[CH:29][CH:28]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH:37]1[CH2:41][CH2:40][C@H:39]([OH:42])[CH2:38]1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C>C1COCC1.C(Cl)Cl>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([O:20][C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)=[CH:18][CH:19]=2)=[O:12])[N:7]([C:27]2[CH:28]=[CH:29][C:30]([CH2:33][C:34]([N:37]3[CH2:41][CH2:40][C@H:39]([OH:42])[CH2:38]3)=[O:36])=[CH:31][CH:32]=2)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2733874(3S)-pyrrolidin-3-olHCID 11496770(4-{3-tert-butyl-5-[({[4-(pyridin-4-yloxy)phenyl]amino}carbonyl)amino]-1H-pyrazol-1-yl}phenyl)acetic acid

Product 1

HCID 11592090N-[3-tert-butyl-1-(4-{2-[(3S)-3-hydroxypyrrolidin-1-yl]-2-oxoethyl}phenyl)-1H-pyrazol-5-yl]-N'-[4-(pyridin-4-yloxy)phenyl]urea

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

A mixture of (4-{3-tert-butyl-5-[({[4-(pyridin-4-yloxy)phenyl]amino}carbonyl)-amino]-1H-pyrazol-1-yl}phenyl)acetic acid (150 mg, 0.31 mmol), (S)-3-pyrrolidinol (54 mg, 0.62 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 71 mg, 0.37 mmol), 1-hydroxybenzotrazole hydrate (HOBT, 50 mg, 0.37 mmol), and triethylamine (0.09 mL, 0.62 mmol) in THF/CH2Cl2 (1/1, 6 mL) was stirred at room temperature overnight. The mixture was evaporated at reduced pressure, and the residue was dissolved in CH2Cl2/MeOH and purified by MPLC (EtOAc/Hexane/MeOH). 1H-NMR (DMSO-d6) δ 9.13 (s, 1H), 8.04 (m, 3H), 7.50-7.34 (m, 6H), 7.07 (d, J=8.9 Hz, 2H), 6.85 (dd, JJ=1.8 Hz, 4.8 Hz, 2H), 6.35 (s, 1H), 4.97 (dd, JJ=3.8 Hz, 44.1 Hz, 1H), 4.27 (broad d, J=30.7 Hz, 1H), 3.70-3.56 (m, 4H), 3.44-3.27 (m, 2H), 1.95-1.73 (m, 2H), 1.27 (s, 9H); MS LC-MS [M+H]+=555.2, RT=2.28 min.

Workup

  1. customThe mixture was evaporated at reduced pressure
  2. dissolutionthe residue was dissolved in CH2Cl2/MeOH
  3. custompurified by MPLC (EtOAc/Hexane/MeOH)

Sources & evidence

ORD record
ord-20f6414ecf42452d81b2fc4e57753c2e
Source dataset
uspto-grants-2010_11
Patent number
US07838524B2

Reaction notes

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