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

HRID 1402193Notes

Reaction equation

HRID 1402193 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]([CH2:25][N:26]3[CH2:31][CH2:30][N:29]([CH3:32])[CH:28]([CH2:33][O:34][Si:35]([CH:42]([CH3:44])[CH3:43])([CH:39]([CH3:41])[CH3:40])[CH:36]([CH3:38])[CH3:37])[CH2:27]3)=[N:23][N:24]=2)[CH:21]=1>CN(C=O)C>[CH3:32][N:29]1[CH2:30][CH2:31][N:26]([CH2:25][C:22]2[N:20]3[CH:21]=[C:16]([O:12][C@H:5]4[C:6]5[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=5)[C@@H:2]([NH2:1])[CH2:3][CH2:4]4)[CH:17]=[CH:18][C:19]3=[N:24][N:23]=2)[CH2:27][CH:28]1[CH2:33][O:34][Si:35]([CH:39]([CH3:41])[CH3:40])([CH:36]([CH3:38])[CH3:37])[CH:42]([CH3:44])[CH3:43]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 866870556-Fluoro-3-(4-methyl-3-triisopropylsilanyloxymethyl-piperazin-1-ylmethyl)-[1,2,4]triazolo[4,3-a]pyridine

Product 1

HCID 86687056(1S,4R)-4-[3-(4-Methyl-3-triisopropylsilanyloxymethyl-piperazin-1-ylmethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Intermediate A (115.4 mg, 0.71 mmol) was added to a mixture of NaH (60% in mineral oil, 87.2 mg, 2.18 mmol) in DMF (4 mL) at RT and stirred for 15 min. Intermediate 56d (237 mg, 0.54 mmol) was then added and the resulting mixture heated to 60° C. for 2 h. After cooling, the reaction was quenched with sat. aq. NH4Cl solution. The mixture was diluted with water and extracted with EtOAc. The combined organic extracts were washed with sat. aq. NaHCO3 solution and brine, and concentrated in vacuo. The resulting residue was loaded onto an SCX-2 cartridge, washed with MeOH then eluted with 1M NH3 in MeOH; concentration in vacuo gave the title compound as a brown residue (91 mg, 29%). LCMS (Method 3): Rt 3.08 min, m/z 579 [MH+].

Workup

  1. temperatureAfter cooling
  2. customthe reaction was quenched with sat. aq. NH4Cl solution
  3. additionThe mixture was diluted with water
  4. extractionextracted with EtOAc
  5. washThe combined organic extracts were washed with sat. aq. NaHCO3 solution and brine
  6. concentrationconcentrated in vacuo
  7. washwashed with MeOH
  8. washthen eluted with 1M NH3 in MeOH
  9. concentrationconcentration in vacuo

Sources & evidence

ORD record
ord-85fd631531ff4a8a8f0aee834a8a92b6
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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