Water → HCID 53251521, compound

HRID 473410Notes

Reaction equation

HRID 473410 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6](Cl)[N:5]=[CH:4][N:3]=1.OC(C(F)(F)F)=O.[F:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[C:25]1[C:34]([CH:35]([NH2:37])[CH3:36])=[CH:33][C:32]2[C:27](=[CH:28][CH:29]=[CH:30][N:31]=2)[N:26]=1.CCN(C(C)C)C(C)C.O>C(O)CCC>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:37][CH:35]([C:34]2[C:25]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=3[F:18])=[N:26][C:27]3[C:32]([CH:33]=2)=[N:31][CH:30]=[CH:29][CH:28]=3)[CH3:36])[N:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 122782624-Amino-6-chloropyrimidine-5-carbonitrileHCID 86654698HCID 86654698, compound

Product 1

HCID 53251521HCID 53251521, compound

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4-amino-6-chloro-5-pyrimidinecarbonitrile (0.045 g, 0.288 mmol), 1-(2-(2-fluorophenyl)-1,5-naphthyridin-3-yl)ethanamine TFA salt (0.110 g, 0.288 mmol), and n,n-diisopropylethylamine (0.251 mL, 1.44 mmol) in butan-1-ol (2.88 mL) was stirred at 120° C. After 5 h, the mixture was removed from the heat and cooled to room temperature. After cooling, the mixture was concentrated under reduced pressure to give brown syrup. To the residue was added water (30 mL) and the mixture was sonicated. The resulting precipitate was collected by filtration, washed with water (20 mL), and dried to give the desired product as a yellow solid. The solid was purified by column chromatography on a 40 g of Redi-Sep™ column using 0 to 100% gradient of CH2Cl2:MeOH:NH4OH (89:9:1) in CH2Cl2 over 14 min and then 100% isocratic of CH2Cl2:MeOH:NH4OH (89:9:1) for 14 min as eluent to give a yellow solid. The yellow solid was suspended in EtOAc-hexane (1:1) and filtered to give 4-amino-6-((1-(2-(2-fluorophenyl)-1,5-naphthyridin-3-yl)ethyl)amino)-5-pyrimidinecarbonitrile as a light yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 9.03 (1H, dd, J=4.2, 1.7 Hz), 8.68 (1H, s), 8.41 (1H, ddd, J=8.6, 1.6, 0.8 Hz), 7.85 (1H, d, J=7.2 Hz), 7.73-7.81 (2H, m), 7.58 (1H, br. s.), 7.45-7.53 (1H, m), 7.26-7.37 (2H, m), 7.17 (2H, br. s.), 5.24-5.36 (1H, m), 1.52 (3H, d, J=7.0 Hz); LC-MS (ESI) m/z 386.0 [M+H]+.

Workup

  1. customthe mixture was removed from the
  2. temperatureheat
  3. temperaturecooled to room temperature
  4. temperatureAfter cooling
  5. concentrationthe mixture was concentrated under reduced pressure
  6. customto give brown syrup
  7. customthe mixture was sonicated
  8. filtrationThe resulting precipitate was collected by filtration
  9. washwashed with water (20 mL)
  10. customdried

Sources & evidence

ORD record
ord-e5a5d7f06b004067a24b713cc347ad55
Source dataset
uspto-grants-2014_01
Patent number
US08633313B2

Reaction notes

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