Sodium hydride → (1S,4R)-4-[3-(2,6-Dichloro-phenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

HRID 572103Notes

Reaction equation

HRID 572103 reaction equation
[NH2:1][C@@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C@H:5]([OH:12])[CH2:4][CH2:3]1.[H-].[Na+].[Cl:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[C:17]=1[C:23]1[N:27]2[CH:28]=[C:29](F)[CH:30]=[CH:31][C:26]2=[N:25][N:24]=1>CN(C=O)C>[Cl:22][C:18]1[CH:19]=[CH:20][CH:21]=[C:16]([Cl:15])[C:17]=1[C:23]1[N:27]2[CH:28]=[C:29]([O:12][C@H:5]3[C:6]4[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=4)[C@@H:2]([NH2:1])[CH2:3][CH2:4]3)[CH:30]=[CH:31][C:26]2=[N:25][N:24]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 848195623-(2,6-Dichlorophenyl)-6-fluoro-[1,2,4]triazolo[4,3-a]pyridineHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-ol

Product 1

HCID 86686715(1S,4R)-4-[3-(2,6-Dichloro-phenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamineYield 33%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Intermediate 1d (404 mg, 2.48 mmol) was added to a stirred solution of sodium hydride (60% in mineral oil, 298 mg, 7.44 mmol) in anhydrous DMF (15 mL) at RT under an argon atmosphere. The reaction mixture was stirred at RT for 15 min, then Intermediate 26c (0.70 g, 2.48 mmol) was added, and stirring at 60° C. was continued for 1 h. After cooling, the reaction mixture was quenched by careful addition of a saturated aqueous solution of NH4Cl and water (1:1) and extracted with EtOAc (×3). The combined organic layers were washed with a saturated aqueous solution of NaHCO3 followed by brine, dried and concentrated in vacuo. The resultant residue was purified by FCC, using 0-20% [2M NH3 in MeOH] in DCM to afford the title compound (345 mg, 33%) as a brown residue. LCMS (Method 3): Rt 2.34 min, m/z 425, 427. [MH+].

Workup

  1. stirringstirring at 60° C.
  2. waitwas continued for 1 h
  3. temperatureAfter cooling
  4. customthe reaction mixture was quenched by careful addition of a saturated aqueous solution of NH4Cl and water (1:1)
  5. extractionextracted with EtOAc (×3)
  6. washThe combined organic layers were washed with a saturated aqueous solution of NaHCO3
  7. customdried
  8. concentrationconcentrated in vacuo
  9. customThe resultant residue was purified by FCC

Sources & evidence

ORD record
ord-4967a4340c804ef69a871aaaa4125fc1
Source dataset
uspto-grants-2015_05
Patent number
US09029373B2

Reaction notes

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