Sodium hydride → HCID 86687135, compound

HRID 630847Notes

Reaction equation

HRID 630847 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[CH2:30][CH2:29][CH2:28][N:27]([CH3:31])[CH2:26]3)=[N:23][N:24]=2)[CH:21]=1>CN(C=O)C>[CH3:31][N:27]1[CH2:28][CH2:29][CH2:30][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)[CH2:26]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 86687134HCID 86687134, compound

Product 1

HCID 86687135HCID 86687135, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of Intermediate A (196 mg, 1.20 mmol) in dry DMF (3 mL) at RT under N2 was added NaH (60% dispersion in oil, 80 mg, 2.00 mmol) and the resulting opaque brown solution stirred for 45 min. A solution of Intermediate 88d (234 mg, 1.00 mmol) in dry DMF (2 mL) was added and the resulting dark brown solution stirred at 60° C. for 90 min. The cooled solution was concentrated in vacuo, redissolved in MeOH (2 mL) and AcOH (0.1 mL), applied to and SCX-2 cartridge and washed with MeOH (75 mL). The product was eluted with 2M NH3 in MeOH (60 mL); concentration in vacuo left a dark brown solid. FCC, using 3-13% [2M NH3 in MeOH] in DCM, gave the title compound as a light brown solid after freeze-drying (280 mg, 74%). LCMS (Method 3): Rt 0.44 min, m/z 378 [MH+].

Workup

  1. stirringthe resulting dark brown solution stirred at 60° C. for 90 min
  2. concentrationThe cooled solution was concentrated in vacuo
  3. dissolutionredissolved in MeOH (2 mL)
  4. washwashed with MeOH (75 mL)
  5. washThe product was eluted with 2M NH3 in MeOH (60 mL)
  6. concentrationconcentration in vacuo
  7. waitleft a dark brown solid

Sources & evidence

ORD record
ord-652c38c57f8a4704a5ffbe913b4c00ce
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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