Sodium hydride → HCID 86687103, compound

HRID 2282537Notes

Reaction equation

HRID 2282537 reaction equation
[H-].[Na+].[NH2:3][C@@H:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C@H:7]([OH:14])[CH2:6][CH2:5]1.F[C:16]1[CH:17]=[CH:18][C:19]2[N:20]([C:22]([C:25]([CH3:32])([N:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)[CH3:26])=[N:23][N:24]=2)[CH:21]=1>CN(C=O)C>[CH3:32][C:25]([C:22]1[N:20]2[CH:21]=[C:16]([O:14][C@H:7]3[C:8]4[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=4)[C@@H:4]([NH2:3])[CH2:5][CH2:6]3)[CH:17]=[CH:18][C:19]2=[N:24][N:23]=1)([N:27]1[CH2:28][CH2:29][CH2:30][CH2:31]1)[CH3:26]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 86687102HCID 86687102, compound

Product 1

HCID 86687103HCID 86687103, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To a suspension of NaH (60% in mineral oil, 135 mg, 3.37 mmol) in DMF (4.50 mL) was added Intermediate A (137 mg, 0.84 mmol) and the reaction stirred for 20 min. Intermediate 80b (209 mg, 0.84 mmol) was added in DMF (1.50 mL) and the reaction heated to 60° C. for 1 h. The reaction was cooled and quenched by dropwise addition of methanol, before being diluted with methanol and loaded onto an SCX-2 cartridge, which was washed with MeOH and product eluted with 2M NH3 in MeOH. The resulting residue was purified by FCC, using 0-10% [2M NH3 in MeOH] in DCM, to give the title compound (180 mg, 55%). LCMS (Method 4): Rt 0.31, m/z 392.2 [MH+].

Workup

  1. temperatureThe reaction was cooled
  2. customquenched by dropwise addition of methanol
  3. additionbefore being diluted with methanol
  4. washwas washed with MeOH and product
  5. washeluted with 2M NH3 in MeOH
  6. customThe resulting residue was purified by FCC

Sources & evidence

ORD record
ord-0212c594fcf94c38b0e892cce68edccb
Source dataset
uspto-grants-2015_09
Patent number
US09139584B2

Reaction notes

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