N-{3-[5-(2-Chloro-4-pyrimidinyl)-2-(1-pyrrolidinyl)-1,3-oxazol-4-yl]phenyl}-2,6-difluorobenzenesulfonamide → 2,6-Difluoro-N-{3-[5-{2-[(2-methylpropyl)amino]-4-pyrimidinyl}-2-(1-pyrrolidinyl)-1,3-oxazol-4-yl]phenyl}benzenesulfonamide

HRID 1961963Notes

Reaction equation

HRID 1961963 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[O:12][C:11]([N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[C:18]2[CH:19]=[C:20]([NH:24][S:25]([C:28]3[C:33]([F:34])=[CH:32][CH:31]=[CH:30][C:29]=3[F:35])(=[O:27])=[O:26])[CH:21]=[CH:22][CH:23]=2)[CH:5]=[CH:4][N:3]=1>C(N)C(C)C>[F:35][C:29]1[CH:30]=[CH:31][CH:32]=[C:33]([F:34])[C:28]=1[S:25]([NH:24][C:20]1[CH:21]=[CH:22][CH:23]=[C:18]([C:9]2[N:10]=[C:11]([N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[O:12][C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:10][CH2:9][CH:18]([CH3:19])[CH3:23])[N:7]=2)[CH:19]=1)(=[O:27])=[O:26]

Participants

3

Reactant 1

HCID 57990047N-{3-[5-(2-Chloro-4-pyrimidinyl)-2-(1-pyrrolidinyl)-1,3-oxazol-4-yl]phenyl}-2,6-difluorobenzenesulfonamide

Product 1

HCID 579900402,6-Difluoro-N-{3-[5-{2-[(2-methylpropyl)amino]-4-pyrimidinyl}-2-(1-pyrrolidinyl)-1,3-oxazol-4-yl]phenyl}benzenesulfonamideYield 138.3%

Reagents, catalysts & solvents 1

HCID 6558IsobutylamineSolvent

Conditions

Temperature
45 °C

Procedure

To a 8 mL vial N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(1-pyrrolidinyl)-1,3-oxazol-4-yl]phenyl}-2,6-difluorobenzenesulfonamide (0.100 g, 0.193 mmol) was taken up in isobutylamine (2 mL) to give a yellow solution. Vial was capped and heated to 45° C. for 2 h. The solvent was removed and residue was purified via Gilson Acidic HPLC (10 to 90% gradient, Acetonitrile/H2O+TFA; C18 column). Desired fractions were diluted with EtOAc and washed with saturated aq. NaHCO3, dried over Na2SO4 and solvent removed to give title compound as a yellow solid (0.074 g). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.93 (s, 1H), 8.18 (d, J=5.1 Hz, 1H), 7.81 (br. s., 1H), 7.59-7.73 (m, 2H), 7.24 (t, J=9.1 Hz, 3H), 7.14 (d, J=7.9 Hz, 1H), 6.97 (t, J=5.7 Hz, 1H), 6.57 (d, J=1.6 Hz, 1H), 3.52 (t, J=6.3 Hz, 4H), 2.76-2.90 (m, 1H), 1.92-2.01 (m, 4H), 0.55-0.94 (m, 6H). MS-ESI m/z 555 (M+H).

Workup

  1. customto give a yellow solution
  2. customVial was capped
  3. customThe solvent was removed
  4. customresidue was purified via Gilson Acidic HPLC (10 to 90% gradient, Acetonitrile/H2O+TFA; C18 column)
  5. additionDesired fractions were diluted with EtOAc
  6. washwashed with saturated aq. NaHCO3
  7. dry with materialdried over Na2SO4 and solvent
  8. customremoved

Sources & evidence

ORD record
ord-3dff84562f284b08b3dd78d0d5821f29
Source dataset
uspto-grants-2013_04
Patent number
US08415345B2

Reaction notes

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