Hydrochloric Acid → (2S,5R)-2-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one

HRID 626918Notes

Reaction equation

HRID 626918 reaction equation
Cl.[CH2:2]([O:4][C:5]1[CH:6]=[CH:7][C:8]([F:29])=[C:9]([C:11]2[CH:16]=[C:15]([CH3:17])[N:14]=[C:13]([C:18]3[CH2:22][CH2:21][C@:20]4([CH2:26][CH2:25][N:24]([CH3:27])[C:23]4=[O:28])[N:19]=3)[N:12]=2)[CH:10]=1)[CH3:3].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH2:2]([O:4][C:5]1[CH:6]=[CH:7][C:8]([F:29])=[C:9]([C:11]2[CH:16]=[C:15]([CH3:17])[N:14]=[C:13]([C@@H:18]3[CH2:22][CH2:21][C@:20]4([CH2:26][CH2:25][N:24]([CH3:27])[C:23]4=[O:28])[NH:19]3)[N:12]=2)[CH:10]=1)[CH3:3]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 5049666Sodium triacetoxyborohydrideHCID 90015243(5R)-2-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]non-1-en-6-one

Product 1

HCID 72548571(2S,5R)-2-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-oneYield 28.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Concentrated aq. HCl (75.18 μL, 0.88 mmol) was added to a solution of the (5R)-2-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]non-1-en-6-one (which may be prepared as described in Description 20) (335 mg, 0.88 mmol) in DCM (20 mL) at 0° C. Finally, sodium triacetoxyborohydride (556.96 mg, 2.63 mmol) was added in a single portion and the resulting mixture was stirred for 90 mins. The reaction was quenched by the addition of sat. Na2CO3 and the resultant mixture was stirred for 5 mins. The phases were separated, the organic layer was dried (Na2SO4) and the solvent was evaporated to afford a brown oil. The material was purified using a Biotage SP4 with a 25 g SNAP cartridge, eluting with 0 to 20% MeOH/EtOAc over 20 column volumes. A partial separation was achieved. Faster running fractions were collected and evaporated to afford (2S,5R)-2-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one as a light brown oil (97 mg)

Workup

  1. customThe reaction was quenched by the addition of sat. Na2CO3
  2. stirringthe resultant mixture was stirred for 5 mins
  3. customThe phases were separated
  4. dry with materialthe organic layer was dried (Na2SO4)
  5. customthe solvent was evaporated
  6. customto afford a brown oil
  7. customThe material was purified
  8. washeluting with 0 to 20% MeOH/EtOAc over 20 column volumes
  9. customA partial separation
  10. customwere collected
  11. customevaporated

Sources & evidence

ORD record
ord-f7d0e88ef3a3410f84f7a266849f2362
Source dataset
uspto-grants-2016_04
Patent number
US09309254B2

Reaction notes

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