Ammonia → HCID 86687122, compound

HRID 2285113Notes

Reaction equation

HRID 2285113 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH:3]1[C:9]1[N:13]2[CH:14]=[C:15](F)[CH:16]=[CH:17][C:12]2=[N:11][N:10]=1.[NH2:19][C@@H:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C@H:23]([OH:30])[CH2:22][CH2:21]1.[H-].[Na+].N>CN(C=O)C.CO.C(Cl)Cl>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH:3]1[C:9]1[N:13]2[CH:14]=[C:15]([O:30][C@H:23]3[C:24]4[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=4)[C@@H:20]([NH2:19])[CH2:21][CH2:22]3)[CH:16]=[CH:17][C:12]2=[N:11][N:10]=1

Participants

8

Reactant 4

HCID 222AmmoniaHCID 24758Sodium hydrideHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 86687123HCID 86687123, compound

Product 1

HCID 86687122HCID 86687122, compoundYield 66.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of Intermediate 86c (100 mg, 0.40 mmol) and Intermediate A (79 mg, 0.40 mmol) in DMF (3 mL) was added NaH (60% in mineral oil, 56 mg, 1.4 mmol) portion-wise. The mixture was stirred at 60° C. for 1.5 h then allowed to cool to RT. The mixture was carefully quenched by pouring into MeOH (10 mL) then applied to an SCX-2 cartridge and washed with MeOH. The product was eluted with 2M NH3 in MeOH; concentration in vacuo gave a residue. FCC, using 0-20% [2M NH3 in MeOH] in DCM, gave the title compound as a brown oil (104 mg, 66%). LCMS (Method 4): Rt 0.26, m/z 393 [MH+].

Workup

  1. temperatureto cool to RT
  2. customThe mixture was carefully quenched
  3. additionby pouring into MeOH (10 mL)
  4. washwashed with MeOH
  5. washThe product was eluted with 2M NH3 in MeOH
  6. concentrationconcentration in vacuo
  7. customgave a residue

Sources & evidence

ORD record
ord-e5a2301b55604cefbd455fd046350e3c
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

Loading…