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

HRID 2282610Notes

Reaction equation

HRID 2282610 reaction equation
[H-].[Na+].[NH2:3][C@@H:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C@H:7]([OH:14])[CH2:6][CH2:5]1.F[C:16]1[CH:17]=[CH:18][C:19]2[N:20]([C:22]([C:25]3([N:30]([CH3:32])[CH3:31])[CH2:29][CH2:28][CH2:27][CH2:26]3)=[N:23][N:24]=2)[CH:21]=1>CN(C=O)C>[CH3:31][N:30]([CH3:32])[C:25]1([C:22]2[N:20]3[CH:21]=[C:16]([O:14][C@H:7]4[C:8]5[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=5)[C@@H:4]([NH2:3])[CH2:5][CH2:6]4)[CH:17]=[CH:18][C:19]3=[N:24][N:23]=2)[CH2:29][CH2:28][CH2:27][CH2:26]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 86687160[1-(6-Fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-cyclopentyl]-dimethyl-amine

Product 1

HCID 86687161(1S,4R)-4-[3-(1-Dimethylamino-cyclopentyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamineYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To a suspension of sodium hydride (60% in mineral oil, 133 mg, 3.34 mmol) in DMF (5 mL) was added Intermediate A (136 mg, 0.83 mmol) and the reaction mixture was stirred for 20 min. A solution of Intermediate 99c (207 mg, 0.83 mmol) in DMF (3 mL) was added and the reaction mixture was heated at 60° C. for 90 min. After cooling, the reaction mixture was quenched by careful addition of MeOH and then loaded onto an SCX cartridge. The cartridge was washed with MeOH and the product eluted with 2M NH3 in MeOH. The product containing fractions were concentrated in vacuo and the resultant residue was purified by FCC on silica, using a gradient of 0-10% (2M NH3 in MeOH) in DCM, to give the title compound (211 mg, 65%). LCMS (Method 4): Rt 1.49 min, m/z 392 [MH+].

Workup

  1. temperatureAfter cooling
  2. customthe reaction mixture was quenched by careful addition of MeOH
  3. washThe cartridge was washed with MeOH
  4. washthe product eluted with 2M NH3 in MeOH
  5. additionThe product containing fractions
  6. concentrationwere concentrated in vacuo
  7. customthe resultant residue was purified by FCC on silica

Sources & evidence

ORD record
ord-4f9dd1ccacb5428b80e1c7266057503b
Source dataset
uspto-grants-2015_09
Patent number
US09139584B2

Reaction notes

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