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Ammonia → (1S,4S)-4-[3-((S)-2-Methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

HRID 631011
Notes
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Reaction equation

HRID 631011 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.[Na].F[C:15]1[CH:16]=[CH:17][C:18]2[N:19]([C:21]([N:24]3[CH2:29][CH2:28][CH2:27][CH2:26][C@@H:25]3[CH3:30])=[N:22][N:23]=2)[CH:20]=1.N>CN(C=O)C.CO.C(Cl)Cl>[CH3:30][C@H:25]1[CH2:26][CH2:27][CH2:28][CH2:29][N:24]1[C:21]1[N:19]2[CH:20]=[C:15]([O:12][C@@H:5]3[C:6]4[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=4)[C@@H:2]([NH2:1])[CH2:3][CH2:4]3)[CH:16]=[CH:17][C:18]2=[N:23][N:22]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 222AmmoniaHCID 5360545SodiumHCID 86686682(1S,4S)-4-amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 866871056-Fluoro-3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridine

Product 1

HCID 86687322(1S,4S)-4-[3-((S)-2-Methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamineYield 47.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of Intermediate B (232 mg, 1.6 mmol) in dry DMF (10 mL) under N2 was added sodium (60% dispersion in oil, 320 mg, 8.0 mmol) and the resulting opaque brown solution was stirred at RT for 45 min (CARE: gas evolution). A solution of Intermediate 81c (342 mg, 1.46 mmol) in dry DMF (7 mL) was added and the dark brown solution stirred at 60° C. under N2 for 90 min. The cooled solution was concentrated in vacuo, redissolved in MeOH (3 mL) and then applied to an SCX-2 cartridge (20 g), washing with MeOH (50 mL). The product was eluted with 2M NH3 in MeOH (50 mL); concentration in vacuo gave a dark brown solid. FCC, using 0-10% [2M NH3 in MeOH] in DCM, gave the title compound as a pale brown foam (262 mg, 45%). LCMS (Method 3): Rt 2.30 min, m/z 378 [MH+].

Workup

  1. stirringthe dark brown solution stirred at 60° C. under N2 for 90 min
  2. concentrationThe cooled solution was concentrated in vacuo
  3. dissolutionredissolved in MeOH (3 mL)
  4. washwashing with MeOH (50 mL)
  5. washThe product was eluted with 2M NH3 in MeOH (50 mL)
  6. concentrationconcentration in vacuo
  7. customgave a dark brown solid

Sources & evidence

ORD record
ord-b9fa1b01c3664b48a3822bd9b64578fb
Source dataset
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09315503B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes