1-Pyrrolidineethanamine → 4-{3-tert-Butyl-5-[({[4-(pyridin-4-yloxy)-phenyl]amino}carbonyl)amino]-1H-pyrazol-1-yl}-N-(2-pyrrolidin-1-ylethyl)benzamide

HRID 1174859Notes

Reaction equation

HRID 1174859 reaction equation
[N:1]1([CH2:6][CH2:7][NH2:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.C[Al](C)C.C[O:14][C:15](=O)[C:16]1[CH:21]=[CH:20][C:19]([N:22]2[C:26]([NH:27][C:28]([NH:30][C:31]3[CH:36]=[CH:35][C:34]([O:37][C:38]4[CH:43]=[CH:42][N:41]=[CH:40][CH:39]=4)=[CH:33][CH:32]=3)=[O:29])=[CH:25][C:24]([C:44]([CH3:47])([CH3:46])[CH3:45])=[N:23]2)=[CH:18][CH:17]=1>ClCCCl>[C:44]([C:24]1[CH:25]=[C:26]([NH:27][C:28]([NH:30][C:31]2[CH:32]=[CH:33][C:34]([O:37][C:38]3[CH:43]=[CH:42][N:41]=[CH:40][CH:39]=3)=[CH:35][CH:36]=2)=[O:29])[N:22]([C:19]2[CH:18]=[CH:17][C:16]([C:15]([NH:8][CH2:7][CH2:6][N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)=[O:14])=[CH:21][CH:20]=2)[N:23]=1)([CH3:47])([CH3:45])[CH3:46]

Participants

5

Reactant 3

HCID 13441-PyrrolidineethanamineHCID 16682925TrimethylaluminumHCID 536301834-(3-Tert-butyl-5-{3-[4-(pyridin-4-yloxy)phenyl]ureido}-pyrazol-1-yl)benzoic acid methyl ester

Product 1

HCID 117138764-{3-tert-Butyl-5-[({[4-(pyridin-4-yloxy)-phenyl]amino}carbonyl)amino]-1H-pyrazol-1-yl}-N-(2-pyrrolidin-1-ylethyl)benzamideYield 29%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

To a solution of 2-pyrrolidin-1-yl-ethylamine in DCE was added trimethyl aluminum (1.03 mmol, 0.51 mL of 2N solution in DCM). After the reaction was stirred at ambient temperature for 30 minutes, a solution of 4-(3-tert-butyl-5-{3-[4-(pyridin-4-yloxy)phenyl]ureido}pyrazol-1-yl}benzoic acid methyl ester (100 mg, 0.21 mmol) in DCE was added, and the reaction mixture was stirred at 80° C. for 16 h. The reaction mixture was quenched with two drops of water, dried over MgSO4, filtered, and evaporated at reduced pressure. Purification using MPLC (eluting with 15% NH3 in MeOH (2N)/EtOAc) afforded 34 mg (29%) of the title compound. 1H-NMR (acetone-d6) δ 8.43 (d, J=9.0 Hz, 2H), 7.94 (d, J=9.0 Hz, 2H), 7.69 (d, J=9.0 Hz, 2H), 7.60 (d, J=9.0 Hz, 2H), 7.07 (d, J=9.0 Hz, 2H), 6.84 (d, J=4.0 Hz, 2H), 6.48 (s, 1H), 3.52 (t, J=7.5 Hz, 2H), 2.67 (t, J=3.0 Hz, 2H), 2.50 to 2.64 (m, 4H), 1.70 to 1.72 (m, 4H), 1.31 (s, 9H); MS LC-MS [M+H]+=568, RT=2.48 min.

Workup

  1. stirringthe reaction mixture was stirred at 80° C. for 16 h
  2. customThe reaction mixture was quenched with two drops of water
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated at reduced pressure
  6. customPurification
  7. washMPLC (eluting with 15% NH3 in MeOH (2N)/EtOAc)

Sources & evidence

ORD record
ord-e0179b90f6694fa0972f5a8affcfc457
Source dataset
uspto-grants-2010_11
Patent number
US07838524B2

Reaction notes

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