Triethylamine → N-(4-{3-tert-Butyl-5-[({[4-(pyridin-4-yloxy)-phenyl]amino}carbonyl)amino]-1H-pyrazol-1-yl}phenyl)-3-methoxypropanamide

HRID 221894Notes

Reaction equation

HRID 221894 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([NH:13][C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=4)=[CH:19][CH:18]=3)=[O:15])=[CH:11][C:10]([C:30]([CH3:33])([CH3:32])[CH3:31])=[N:9]2)=[CH:4][CH:3]=1.[CH3:34][O:35][CH2:36][CH2:37][C:38](Cl)=[O:39].CCN(CC)CC>C1COCC1>[C:30]([C:10]1[CH:11]=[C:12]([NH:13][C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]3[CH:25]=[CH:26][N:27]=[CH:28][CH:29]=3)=[CH:19][CH:18]=2)=[O:15])[N:8]([C:5]2[CH:6]=[CH:7][C:2]([NH:1][C:38](=[O:39])[CH2:37][CH2:36][O:35][CH3:34])=[CH:3][CH:4]=2)[N:9]=1)([CH3:33])([CH3:32])[CH3:31]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27597283-Methoxypropanoyl chlorideHCID 536301891-[2-(4-aminophenyl)-5-tert-butyl-2H-pyrazol-3-yl]-3-[4-(pyridin-4-yloxy)phenyl]urea

Product 1

HCID 11562765N-(4-{3-tert-Butyl-5-[({[4-(pyridin-4-yloxy)-phenyl]amino}carbonyl)amino]-1H-pyrazol-1-yl}phenyl)-3-methoxypropanamideYield 21.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-[2-(4-aminophenyl)-5-tert-butyl-2H-pyrazol-3-yl]-3-[4-(pyridin-4-yloxy)phenyl]urea (200 mg, 0.45 mmol) and 3-methoxypropionyl chloride (55 mg, 0.45 mmol) in anhydrous THF (5 mL) was added Et3N (69 mg, 0.68 mmol). The reaction was stirred at room temperature for 7 h, and then partitioned between EtOAc (50 mL) and water (50 mL). The organic layer was washed with brine, dried over Na2SO4, and concentrated at reduced pressure. The residue was purified by MPLC (1:1 hexanes/EtOAc) to give 51 mg (21%) of the desired product. 1H-NMR (DMSO-d6) δ 10.16 (s, 1H), 9.14 (s, 1H), 8.42 (d, J=4.8 Hz, 2H), 8.34 (s, 1H), 7.74 (d, J=6.9 Hz, 2H), 7.48 (d, J=6.9 Hz, 2H), 7.43 (d, J=8.7 Hz, 2H), 7.08 (d, J=6.6 Hz, 2H), 6.88 (d, J=5.4 Hz, 2H), 6.35 (s, 1H), 3.63 (t, J=6.0 Hz, 2H), 3.33 (s, 3H), 2.57 (t, J=6.0 Hz, 2H), 1.27 (s, 9H); MS LC-MS [M+H]+=529, RT=2.20 min.

Workup

  1. custompartitioned between EtOAc (50 mL) and water (50 mL)
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated at reduced pressure
  5. customThe residue was purified by MPLC (1:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-966582ea245a48d9aac5ba318dfc1c07
Source dataset
uspto-grants-2012_06
Patent number
US08207166B2

Reaction notes

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