Acetic Acid → (1S,4R)-4-[3-(4-Allyloxy-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

HRID 1402197Notes

Reaction equation

HRID 1402197 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+].[CH2:15]([O:18][CH:19]1[CH2:24][CH2:23][N:22]([C:25]2[N:29]3[CH:30]=[C:31](F)[CH:32]=[CH:33][C:28]3=[N:27][N:26]=2)[CH2:21][CH2:20]1)[CH:16]=[CH2:17].CC(O)=O>CN(C=O)C>[CH2:15]([O:18][CH:19]1[CH2:20][CH2:21][N:22]([C:25]2[N:29]3[CH:30]=[C:31]([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:32]=[CH:33][C:28]3=[N:27][N:26]=2)[CH2:23][CH2:24]1)[CH:16]=[CH2:17]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 866870583-(4-Allyloxy-piperidin-1-yl)-6-fluoro-[1,2,4]triazolo[4,3-a]pyridine

Product 1

HCID 86687059(1S,4R)-4-[3-(4-Allyloxy-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamineYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A suspension of Intermediate A (108 mg, 0.661 mmol) and NaH (60% dispersion in oil, 72.1 mg, 180 mmol) in dry DMF (5 mL) at RT under Ar was stirred for 1 h (CARE: gas evolution). A solution of Intermediate 57a (166 mg, 0.601 mmol) in dry DMF (3 mL) was added and the dark brown solution stirred at 60° C. for 90 min. The solution was concentrated in vacuo, and the residue redissolved in MeOH (5 mL) and AcOH (0.171 mL, 3.00 mmol). The solution was applied to an SCX-2 cartridge (10 g) and was washed with MeOH (100 mL). The product was eluted with 2M NH3 in MeOH (75 mL); concentration in vacuo left a dark brown solid. FCC, using 2-8% [2M NH3 in MeOH] in DCM, gave the title compound as a dark brown oil (204 mg, 81%). LCMS (Method 3): Rt 2.34 min, m/z 420 [MH+].

Workup

  1. stirringthe dark brown solution stirred at 60° C. for 90 min
  2. concentrationThe solution was concentrated in vacuo
  3. dissolutionthe residue redissolved in MeOH (5 mL)
  4. washwas washed with MeOH (100 mL)
  5. washThe product was eluted with 2M NH3 in MeOH (75 mL)
  6. concentrationconcentration in vacuo
  7. waitleft a dark brown solid

Sources & evidence

ORD record
ord-dc44924121a048c0800ef5417df6b232
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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