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Water → (1S,4R)-4-[3-(4-Aza-spiro[2.5]oct-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

HRID 2282710
Notes
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Reaction equation

HRID 2282710 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]1[C:17]2([CH2:22][CH2:21][CH2:20][CH2:19][N:18]2[C:23]2[N:27]3[CH:28]=[C:29](F)[CH:30]=[CH:31][C:26]3=[N:25][N:24]=2)[CH2:16]1.O>CN(C=O)C>[CH2:16]1[C:17]2([CH2:22][CH2:21][CH2:20][CH2:19][N:18]2[C:23]2[N:27]3[CH:28]=[C:29]([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:30]=[CH:31][C:26]3=[N:25][N:24]=2)[CH2:15]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 866872653-(4-Aza-spiro[2.5]oct-4-yl)-6-fluoro-[1,2,4]triazolo[4,3-a]pyridine

Product 1

HCID 86687266(1S,4R)-4-[3-(4-Aza-spiro[2.5]oct-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamineYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To an opaque brown solution of Intermediate A (371 mg, 2.28 mmol) in dry DMF (5 mL) under N2 was added sodium hydride (60% dispersion in mineral oil, 273 mg, 6.83 mmol) and the resulting mixture stirred at RT for 30 min. (CARE: gas evolution) A solution of Intermediate 148c (448 mg, 1.82 mmol) in dry DMF (5 mL) was added and the resulting dark brown solution stirred at 60° C. for 1 h. The solution was cooled to RT, then water (0.2 mL) added (CARE: gas evolution) and the mixture concentrated in vacuo. The residue was redissolved in MeOH (10 mL), applied to an SCX-2 cartridge (25 g) and washed with MeOH (100 mL). The product was eluted with 2M NH3 in MeOH (75 mL); concentration in vacuo left a dark brown gum. Flash chromatography (silica 40 g, 4-7% [2M NH3 in MeOH] in DCM) gave the title compound as a pale brown foam (446 mg, 63%). LCMS (Method 3): Rt 2.31 min, m/z 390 [MH+].

Workup

  1. additionwas added
  2. temperatureThe solution was cooled to RT
  3. concentrationthe mixture concentrated in vacuo
  4. dissolutionThe residue was redissolved in MeOH (10 mL)
  5. washwashed with MeOH (100 mL)
  6. washThe product was eluted with 2M NH3 in MeOH (75 mL)
  7. concentrationconcentration in vacuo
  8. waitleft a dark brown gum

Sources & evidence

ORD record
ord-47f373b8f2ae45e4be51c38c451c1237
Source dataset
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09139584B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes