Ammonia → HCID 86687088, compound

HRID 1402234Notes

Reaction equation

HRID 1402234 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]([N:25]3[CH2:30][CH2:29][CH:28]([C:31]([CH3:44])([O:33][Si:34]([CH:41]([CH3:43])[CH3:42])([CH:38]([CH3:40])[CH3:39])[CH:35]([CH3:37])[CH3:36])[CH3:32])[CH2:27][CH2:26]3)=[N:23][N:24]=2)[CH:21]=1.N>CN(C=O)C.CO.C(Cl)Cl>[CH3:32][C:31]([CH:28]1[CH2:27][CH2:26][N: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)[CH2:30][CH2:29]1)([O:33][Si:34]([CH:41]([CH3:43])[CH3:42])([CH:38]([CH3:39])[CH3:40])[CH:35]([CH3:36])[CH3:37])[CH3:44]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 24758Sodium hydrideHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 86687086HCID 86687086, compound

Product 1

HCID 86687088HCID 86687088, compoundYield 30.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of Intermediate A (129 mg, 0.788 mmol) in dry DMF (2 mL) at RT under Ar was added NaH (60% dispersion in oil, 45.0 mg, 1.13 mmol) (CARE: gas evolution) and the resulting opaque brown solution stirred at RT for 45 min. A solution of Intermediate 74b (326 mg, 0.750 mmol) in dry DMF (2 mL) was added and the resulting dark brown solution stirred at 60° C. for 2.5 h. The solution was concentrated in vacuo, redissolved in MeOH (2 mL) and AcOH (0.100 mL), applied to an SCX-2 cartridge and washed with MeOH (100 mL). The product was eluted with 2M NH3 in MeOH (75 mL); concentration in vacuo gave a viscous dark brown oil. FCC, using 1-6% [2M NH3 in MeOH] in DCM, gave the title compound as a viscous brown oil (131 mg, 30%). LCMS (Method 3): Rt 3.53 min, m/z 578 [MH+].

Workup

  1. stirringthe resulting dark brown solution stirred at 60° C. for 2.5 h
  2. concentrationThe solution was concentrated in vacuo
  3. dissolutionredissolved in MeOH (2 mL)
  4. washwashed with MeOH (100 mL)
  5. washThe product was eluted with 2M NH3 in MeOH (75 mL)
  6. concentrationconcentration in vacuo
  7. customgave a viscous dark brown oil

Sources & evidence

ORD record
ord-db1440f5013245b893c95be088bdbcac
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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