Sodium hydride → HCID 53251526, compound

HRID 473420Notes

Reaction equation

HRID 473420 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]([CH2:18][OH:19])=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][N:14]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].[NH2:22][C:23]1[C:28]([C:29]#[N:30])=[C:27](Cl)[N:26]=[CH:25][N:24]=1>CN(C=O)C>[NH2:22][C:23]1[C:28]([C:29]#[N:30])=[C:27]([O:19][CH2:18][C:17]2[C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[N:9][C:10]3[C:15]([CH:16]=2)=[N:14][CH:13]=[CH:12][CH:11]=3)[N:26]=[CH:25][N:24]=1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 122782624-Amino-6-chloropyrimidine-5-carbonitrileHCID 58318598HCID 58318598, compound

Product 1

HCID 53251526HCID 53251526, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (2-(3-fluorophenyl)-1,5-naphthyridin-3-yl)methanol (65 mg, 0.256 mmol) in DMF (1.5 mL) was added sodium hydride (12.3 mg, 0.31 mmol, 60% suspension in oil) and the reaction was stirred at rt for 10 min. After this time 4-amino-6-chloropyrimidine-5-carbonitrile (39.5 mg, 0.256 mmol) was added and the reaction was stirred at rt for 30 min. After this time an additional portion of NaH (12.3 mg, 0.31 mmol, 60% dispersion in oil) was added and the reaction was heated at 50° C. for 2 h and at rt overnight. After this time the reaction was cooled to rt and partitioned between EtOAc (50 mL) and LiCl (20 mL, 1M aq. solution). The separated organic layer was washed with LiCl (20 mL, 1M aq. solution) and then it was dried over MgSO4, filtered and concentrated in vacuo. The mixture was purified by reversed-phase HPLC (10 to 60% acetonitrile in water) to give 4-amino-6-((2-(3-fluorophenyl)-1,5-naphthyridin-3-yl)methoxy)-5-pyrimidinecarbonitrile as a white solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 9.04 (1H, dd, J=4.2, 1.7 Hz), 8.61-8.66 (1H, m), 8.44-8.51 (1H, m), 8.28 (1H, s), 7.71 (1H, dd, J=8.6, 4.1 Hz), 7.36-7.56 (3H, m), 7.21 (1H, tdd, J=8.3, 8.3, 2.7, 1.2 Hz), 5.67 (2H, s), 5.62 (2H, br. s.): LC-MS (ESI) m/z 373.1 [M+H]+.

Workup

  1. stirringthe reaction was stirred at rt for 30 min
  2. temperaturethe reaction was heated at 50° C. for 2 h and at rt overnight
  3. temperatureAfter this time the reaction was cooled to rt
  4. custompartitioned between EtOAc (50 mL) and LiCl (20 mL, 1M aq. solution)
  5. washThe separated organic layer was washed with LiCl (20 mL, 1M aq. solution)
  6. dry with materialit was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe mixture was purified by reversed-phase HPLC (10 to 60% acetonitrile in water)

Sources & evidence

ORD record
ord-c6c6dcc3d62942109e42f7afe2828f13
Source dataset
uspto-grants-2014_01
Patent number
US08633313B2

Reaction notes

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