Water → HCID 53251828, compound

HRID 473432Notes

Reaction equation

HRID 473432 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([CH:22]([NH2:24])[CH3:23])[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[S:18]([CH3:21])(=[O:20])=[O:19])=[N:9]2)=[N:4][CH:3]=1.[NH2:25][C:26]1[C:31]([C:32]#[N:33])=[C:30](Cl)[N:29]=[CH:28][N:27]=1.C(N(C(C)C)CC)(C)C.O>C(O)CCC>[NH2:25][C:26]1[C:31]([C:32]#[N:33])=[C:30]([NH:24][CH:22]([C:7]2[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[S:18]([CH3:21])(=[O:20])=[O:19])=[N:9][C:10]3[C:5]([CH:6]=2)=[N:4][CH:3]=[C:2]([F:1])[CH:11]=3)[CH3:23])[N:29]=[CH:28][N:27]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 122782624-Amino-6-chloropyrimidine-5-carbonitrileHCID 58318590HCID 58318590, compound

Product 1

HCID 53251828HCID 53251828, compound

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of 1-(7-fluoro-2-(2-(methylsulfonyl)phenyl)-1,5-naphthyridin-3-yl)ethanamine (300 mg, 0.86 mmol) and 4-amino-6-chloropyrimidine-5-carbonitrile (135 mg, 0.86 mmol) in n-butanol (5.2 mL) was added diisopropylethyl amine (336 mg, 2.6 mmol) at 25° C. The reaction mixture was stirred for overnight at 110° C. Water was added to the reaction mixture and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated it. 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-(7-fluoro-2-(2-(methylsulfonyl)phenyl)-1,5-naphthyridin-3-yl)ethyl)amino)-5-pyrimidinecarbonitrile: 1H NMR (400 MHz, DMSO-d6): δ 1.380 (d, 3H, J=6.8 Hz), 3.215 (s, 3H), 5.240-5.310 (m, 1H), 7.256 (br s, 2H), 7.718-7.828 (m, 2H), 7.934-7.950 (m, 3H), 8.123 (dd, 1H, J=1.2 Hz, 7.6 Hz), 8.336 (dd, 1H, J=2.4 Hz, 9.6 Hz). 8.678 (s, 1H), 9.117 (d, 1H, J=2.8 Hz); LC-MS (ESI) m/z 464.2 [M+H]+.

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated it
  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-471e7e09b4534b5eaa3ed2d032c7100e
Source dataset
uspto-grants-2014_01
Patent number
US08633313B2

Reaction notes

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