Hydrochloric Acid → 1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-[3-(1-hydroxy-ethyl)-phenyl]-urea

HRID 919515Notes

Reaction equation

HRID 919515 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([C:22]3[N:23]([CH3:28])[N:24]=[CH:25][C:26]=3[Br:27])[CH:15]=2)=[O:12])[CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2].[BH4-].[Na+].Cl.CCOC(C)=O>C(O)C>[Br:27][C:26]1[CH:25]=[N:24][N:23]([CH3:28])[C:22]=1[C:16]1[CH:15]=[C:14]([NH:13][C:11]([NH:10][C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([CH:1]([OH:3])[CH3:2])[CH:5]=2)=[O:12])[CH:19]=[CH:18][C:17]=1[O:20][CH3:21]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 4311764Sodium borohydrideHCID 111782371-(3-Acetyl-phenyl)3-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-urea

Product 1

HCID 117049561-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-[3-(1-hydroxy-ethyl)-phenyl]-ureaYield 63%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Compound 17 (30.2 mg, 0.07 mmol, see Example 1.24) was dissolved in ethanol (5 mL). Sodium Borohydride (3.1 mg, 0.08 mmol) was added under Argon gas. The reaction was stirred overnight and found to be complete by TLC and LC/MS. The mixture was worked up with 1N Hydrogen Chloride solution (10 mL) and EtOAc (2×15 mL). The organic layers were combined and washed with water, dried over Na2SO4, filtered, and the solvent removed under reduced pressure. The residue was then purified by HPLC to afford 19.4 mg (63%) of Compound 94: LCMS m/z (%)=445 (M+H79Br, 25), 447 (M+H81Br, 25). 1H NMR (400 MHz, CDCl3) δ: 7.34 (dd, J1=8 Hz, J2=2 Hz, 1H), 7.26 (s, 1H), 7.20 (s, 1H), 7.14 (s, 1H), 7.11 (d, J=8 Hz, 1H), 7.09 (s, 1H), 7.06 (t, 1H), 6.95 (d, J=4 Hz, 1H), 6.85 (d, J=8 Hz, 1H), 6.76 (d, J=8 Hz, 1H), 4.65 (m, 1H), 3.59 (s, 3H), 3.49 (s, 3H), 1.27 (d, J=4 Hz, 3H).

Workup

  1. washwashed with water
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. customthe solvent removed under reduced pressure
  5. customThe residue was then purified by HPLC

Sources & evidence

ORD record
ord-d33ae6a7df384a21b14680836c028c71
Source dataset
uspto-grants-2016_03
Patent number
US09273035B2

Reaction notes

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