Tetrahydrofuran → HCID 11497404, compound

HRID 221903Notes

Reaction equation

HRID 221903 reaction equation
[NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([NH:14][C:15]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]4[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=4)=[CH:20][CH:19]=3)=[O:16])=[CH:12][C:11]([C:31]([CH3:34])([CH3:33])[CH3:32])=[N:10]2)=[CH:5][CH:4]=1.C(N(CC)C(C)C)(C)C.[CH3:44][O:45][CH2:46][CH2:47]C(Cl)=O.C1C[O:54]CC1>>[C:31]([C:11]1[CH:12]=[C:13]([NH:14][C:15]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]3[CH:26]=[CH:27][N:28]=[CH:29][CH:30]=3)=[CH:20][CH:19]=2)=[O:16])[N:9]([C:6]2[CH:7]=[CH:8][C:3]([CH2:2][NH:1][C:47](=[O:54])[CH2:46][O:45][CH3:44])=[CH:4][CH:5]=2)[N:10]=1)([CH3:34])([CH3:33])[CH3:32]

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 81531DiisopropylethylamineHCID 27597283-Methoxypropanoyl chlorideHCID 11554303HCID 11554303, compound

Product 1

HCID 11497404HCID 11497404, compoundYield 52%

Procedure

To a solution of 1-[2-(4-aminomethyl-phenyl)-5-tert-butyl-2H-pyrazol-3-yl]-3-[4-(pyridin-4-yloxy)phenyl]urea (400 mg, 0.88 mmol) in THF (20 mL) was added N,N-diisopropylethylamine (0.23 mL, 1.31 mmol). A solution of 3-methoxypropionyl chloride (95 mg, 0.88 mmol) in THF (1 mL) was added to the solution at 0° C. under N2 and the reaction mixture was stirred at room temperature for 3 h. The reaction mixture was concentrated at reduced pressure and dissolved in EtOAc (100 mL). The solution was washed with water and brine, dried over Na2SO4, and concentrated at reduced pressure. The residue was purified by MPLC (50:50 hexanes/EtOAc) to give 240 mg (52%) of the desired product. 1H-NMR (DMSO-d6) δ 9.16 (s, 1H), 8.42 to 8.40 (m, 4H), 7.50 to 7.37 (m, 6H), 7.08 (d, J=8.7 Hz, 2H), 6.85 (d, J=6.0 Hz, 2H), 6.34 (s, 1H), 4.33 (d, J=6.0 Hz, 2H), 3.86 (s, 2H), 3.26 (s, 3H), 1.25 (s, 9H); MS LC-MS [M+H]+=529, RT=2.29 min.

Workup

  1. concentrationThe reaction mixture was concentrated at reduced pressure
  2. dissolutiondissolved in EtOAc (100 mL)
  3. washThe solution was washed with water and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated at reduced pressure
  6. customThe residue was purified by MPLC (50:50 hexanes/EtOAc)

Sources & evidence

ORD record
ord-c8bf4cd9774c468ba894bf68d5af110e
Source dataset
uspto-grants-2012_06
Patent number
US08207166B2

Reaction notes

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