Hydrochloric Acid → 8-(2-Chloro-4-fluorophenyl)-2-(1-(2-chloropyridin-4-yl)piperidin-4-ylamino)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-6-ol

HRID 451525

Reaction equation

HRID 451525 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:14][CH:13]([OH:15])[CH2:12][N:11]2[N:16]=[C:17]([NH:19][CH:20]3[CH2:25][CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22][CH2:21]3)[N:18]=[C:10]12.Cl.[Cl:34][C:35]1[CH:40]=[C:39](F)[CH:38]=[CH:37][N:36]=1>>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:14][CH:13]([OH:15])[CH2:12][N:11]2[N:16]=[C:17]([NH:19][CH:20]3[CH2:21][CH2:22][N:23]([C:39]4[CH:38]=[CH:37][N:36]=[C:35]([Cl:34])[CH:40]=4)[CH2:24][CH2:25]3)[N:18]=[C:10]12

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 27827922-Chloro-4-fluoropyridineHCID 67345513tert-Butyl 4-(8-(2-chloro-4-fluorophenyl)-6-hydroxy-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)piperidine-1-carboxylate

Product 1

HCID 583979228-(2-Chloro-4-fluorophenyl)-2-(1-(2-chloropyridin-4-yl)piperidin-4-ylamino)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-6-ol

Conditions

Temperature
80 °C

Procedure

To tert-butyl 4-(8-(2-chloro-4-fluorophenyl)-6-hydroxy-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)piperidine-1-carboxylate (0.05 g, 0.1 mmol) was added HCl (3 mL, 4 N in dioxane) and the reaction stirred for 0.5 hour. The reaction was then concentrated to dryness, the residue redissolved in dimethylacetamide (0.5 mL), triethylamine added until the mixture was basic, followed by the addition of 2-chloro-4-fluoropyridine (0.04 g, 0.3 mmol) and the mixture heated to 80° C. for 1 hour. The reaction was evaporated to dryness, redissolved in ethyl acetate, washed with saturated sodium hydrogen carbonate, water, brine, dried with sodium sulfate and the solvent was evaporated in vacuo. The residue was purified by column chromatography on silica gel using ethyl acetate/MeOH (v/v 1:0 to 95:5) as eluent. The title compound was obtained as a light yellow gum (0.04 g, 76%), an inseparable 1:1 mixture of diasteriomers. MS ISP (m/e): 477.1 [(M+H)+].

Workup

  1. concentrationThe reaction was then concentrated to dryness
  2. dissolutionthe residue redissolved in dimethylacetamide (0.5 mL)
  3. additiontriethylamine added until the mixture
  4. customThe reaction was evaporated to dryness
  5. dissolutionredissolved in ethyl acetate
  6. washwashed with saturated sodium hydrogen carbonate, water, brine
  7. dry with materialdried with sodium sulfate
  8. customthe solvent was evaporated in vacuo
  9. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-c9a49454817f4cbcacb1937f4c8ef68c
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Linked notes

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