Water → HCID 58318592, compound

HRID 473440Notes

Reaction equation

HRID 473440 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[C:20]([CH:21]([NH2:23])[CH3:22])=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][N:17]=2)[N:12]=1)(=[O:4])=[O:3].[NH2:24][C:25]1[C:30]([C:31]#[N:32])=[C:29](Cl)[N:28]=[CH:27][N:26]=1.CCN(C(C)C)C(C)C.O>C(O)CCC>[NH2:24][C:25]1[C:30]([C:31]#[N:32])=[C:29]([NH:23][CH:21]([C:20]2[C:11]([C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=3[S:2]([CH3:1])(=[O:3])=[O:4])=[N:12][C:13]3[C:18]([CH:19]=2)=[N:17][CH:16]=[CH:15][CH:14]=3)[CH3:22])[N:28]=[CH:27][N:26]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 122782624-Amino-6-chloropyrimidine-5-carbonitrileHCID 58318613HCID 58318613, compound

Product 1

HCID 58318592HCID 58318592, compound

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of crude 1-(2-(2-(methylsulfonyl)phenyl)-1,5-naphthyridin-3-yl)ethanamine (600 mg, 1.83 mmol) and 4-amino-6-chloropyrimidine-5-carbonitrile (283 mg, 1.83 mmol) in n-butanol (11 mL) was added Hunig base (709 mg, 5.49 mmol) at 25° C. The reaction mixture was stirred for overnight at 110° C. Water was added to reaction mixture and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on neutral alumina using 0-5% MeOH in DCM. It was further purified by reversed-phase HPLC to give 4-amino-6-((1-(2-(2-(methylsulfonyl)phenyl)-1,5-naphthyridin-3-yl)ethyl)amino)-5-pyrimidine-carbonitrile: 1H NMR (DMSO-d6, 400 MHz) δ 1.387 (d, J=6.8 Hz, 3H), 5.250-5.322 (m, 1H), 7.246 (br s, 2H), 7.735-7.843 (m, 3H), 7.911-7.940 (m, 3H), 8.110-8.129 (m, 1H), 8.395 (d, J=4.4 Hz, 1H), 8.622 (s, 1H), 9.028-9.074 (m, 1H); LC-MS (ESI) m/z 446.0 [M+H]+.

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by column chromatography on neutral alumina using 0-5% MeOH in DCM
  5. customIt was further purified by reversed-phase HPLC

Sources & evidence

ORD record
ord-9448312faa3c4252aec8b8e90ce4cf90
Source dataset
uspto-grants-2014_01
Patent number
US08633313B2

Reaction notes

Loading…