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

HRID 60684Notes

Reaction equation

HRID 60684 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+].F[C:16]1[CH:17]=[CH:18][C:19]2[N:20]([C:22]([N:25]3[CH2:29][CH2:28][CH2:27][C@@H:26]3[CH3:30])=[N:23][N:24]=2)[CH:21]=1>CN(C=O)C>[CH3:30][C@H:26]1[CH2:27][CH2:28][CH2:29][N:25]1[C:22]1[N:20]2[CH:21]=[C:16]([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:17]=[CH:18][C:19]2=[N:24][N:23]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 1177297266-Fluoro-3-((S)-2-methyl-pyrrolidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridine

Product 1

HCID 117729600(1S,4R)-4-[3-((S)-2-Methyl-pyrrolidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamineYield 38.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Intermediate A (318 mg, 1.95 mmol) was dissolved in DMF (1 mL) and sodium hydride (60% dispersion in oil, 125 mg, 3.25 mmol) was added portionwise. The mixture was stirred at RT for 10 min. A solution of Intermediate 78a (357 mg, 1.62 mmol) in DMF (1 mL) was added and the reaction mixture was heated at 60° C. for 1.5 h. The mixture was cooled to RT and partitioned between EtOAc (10 mL) and water (10 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by FCC, using 0-10% [2M NH3 in MeOH] in DCM, to afford the title compound as an orange gum (226 mg, 38%). LCMS (Method 3): Rt 0.42, 2.06 min, m/z 364 [MH+].

Workup

  1. temperaturethe reaction mixture was heated at 60° C. for 1.5 h
  2. temperatureThe mixture was cooled to RT
  3. custompartitioned between EtOAc (10 mL) and water (10 mL)
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-7187df40c0124ca08e69a127694f6401
Source dataset
uspto-grants-2016_09
Patent number
US09440974B2

Reaction notes

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