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

HRID 75574Notes

Reaction equation

HRID 75574 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]([CH:25]([CH3:27])[CH3:26])=[N:23][N:24]=2)[CH:21]=1>CN(C=O)C>[CH:25]([C:22]1[N:20]2[CH:21]=[C:16]([O:14][C@@H:7]3[C:8]4[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=4)[C@@H:4]([NH2:3])[CH2:5][CH2:6]3)[CH:17]=[CH:18][C:19]2=[N:24][N:23]=1)([CH3:27])[CH3:26]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 587839636-Fluoro-3-isopropyl-[1,2,4]triazolo[4,3-a]pyridineHCID 86686682(1S,4S)-4-amino-1,2,3,4-tetrahydronaphthalen-1-ol

Product 1

HCID 86686683(1S,4S)-4-(3-Isopropyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-ylamineYield 111.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of sodium hydride (60% in mineral oil, 1.07 g, 26.8 mmol) in dry DMF (20 mL) at room temperature under nitrogen, Intermediate 5b (1.89 g, 11.6 mmol) was added portionwise over 2 min, and the resulting brown solution was stirred for 20 min. Intermediate 1f (1.60 g, 8.93 mmol) was added, and the solution stirred at 60° C. for 2 h. The dark brown solution was cooled to room temperature and concentrated under vacuum. The residue was purified by SCX-2, washing with MeOH (200 mL) and eluting with 2M NH3 in MeOH, to leave a dark brown foam (3.21 g). Further purification by FCC, using 2-10% [2M NH3 in MeOH] in DCM, gave a brown foam (2.11 g, 76%). 1H NMR (400 MHz, d6-DMSO): 1.37 (3H, d), 1.39 (3H, d), 1.59 (1H, m), 1.91 (1H, m), 2.11 (1H, m), 2.33 (1H, m), 3.58 (1H, sept), 3.96 (1H, dd), 5.55 (1H, dd), 7.18-7.37 (4H, m), 7.51 (1H, d), 7.68 (1H, d), 8.20 (1H, d).

Workup

  1. stirringthe solution stirred at 60° C. for 2 h
  2. concentrationconcentrated under vacuum
  3. customThe residue was purified by SCX-2
  4. washwashing with MeOH (200 mL)
  5. washeluting with 2M NH3 in MeOH

Sources & evidence

ORD record
ord-76f786c6e8a24bd790b93578cb12ef72
Source dataset
uspto-grants-2014_09
Patent number
US08835431B2

Reaction notes

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