Ammonia → HCID 86687145, compound

HRID 2285134Notes

Reaction equation

HRID 2285134 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+].F[C:16]1[CH:17]=[CH:18][C:19]2[N:20]([C:22]([C@@H:25]3[CH2:29][C@@H:28]([F:30])[CH2:27][N:26]3[CH3:31])=[N:23][N:24]=2)[CH:21]=1.N>CN(C=O)C.O.CO.C(Cl)Cl>[F:30][C@H:28]1[CH2:27][N:26]([CH3:31])[C@H:25]([C:22]2[N:20]3[CH:21]=[C:16]([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:17]=[CH:18][C:19]3=[N:24][N:23]=2)[CH2:29]1

Participants

9

Reactant 4

HCID 222AmmoniaHCID 24758Sodium hydrideHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 86687144HCID 86687144, compound

Product 1

HCID 86687145HCID 86687145, compoundYield 51.5%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of Intermediate A (161 mg, 0.99 mmol) in dry DMF (2.5 mL) at RT was added NaH (60% in mineral oil, 108 mg, 2.70 mmol) and the mixture stirred for 15 min. Intermediate 91c (214 mg, 0.89 mmol) in DMF (2.5 mL) was then added and the mixture heated at 60° C. for 1 h. After cooling, the resulting dark brown mixture was diluted with water and extracted with DCM. The combined organics were dried and concentrated in vacuo. The residue was purified by FCC, using 0-10% MeOH in DCM, to give crude product. FCC, using 0-10% (2M NH3 in MeOH) in DCM, gave the title compound as light brown foam (175 mg, 51%). LCMS (Method 3): Rt 0.43 min, m/z 382 [MH+].

Workup

  1. temperatureAfter cooling
  2. extractionextracted with DCM
  3. customThe combined organics were dried
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by FCC
  6. customto give crude product

Sources & evidence

ORD record
ord-f2043fe2f202483f8ac2937b8c3a98a2
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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