Hydrochloric Acid → 4-{[(3R,4S)-4-amino-3-hydroxy-1-piperidinyl]methyl}-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one

HRID 15316Notes

Reaction equation

HRID 15316 reaction equation
CC([N:5]([C@H:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH:16]2[C:20]3=[C:21]([F:29])[CH:22]=[N:23][C:24]4[CH:25]=[CH:26][C:27](=[O:28])[N:18]([C:19]=43)[CH2:17]2)[CH2:11][C@H:10]1[OH:30])C(=O)[O-])(C)C.Cl>C(O)(=O)C.O1CCOCC1>[NH2:5][C@H:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH:16]2[C:20]3=[C:21]([F:29])[CH:22]=[N:23][C:24]4[CH:25]=[CH:26][C:27](=[O:28])[N:18]([C:19]=43)[CH2:17]2)[CH2:11][C@H:10]1[OH:30]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 131728170racemic 1,1-dimethylethyl{(3R,4S)-1-[(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-3-hydroxy-4-piperidinyl}carbamate

Product 1

HCID 686861754-{[(3R,4S)-4-amino-3-hydroxy-1-piperidinyl]methyl}-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-oneYield 87.2%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of racemic 1,1-dimethylethyl{(3R,4S)-1-[(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-3-hydroxy-4-piperidinyl}carbamate (200 mg) in acetic acid (6 ml) was treated with a 4M solution of HCl in 1,4-dioxane (2 ml), stirred 2 h at room temperature and evaporated to dryness. A part solution/part suspension of this material in dichloromethane (8.5 ml) and methanol (1.5 ml) was treated with MP-carbonate resin (obtained from Argonaut Technologies) (1.2 g), stirred for 3 h, filtered and the resin washed well with 1:1 dichloromethane/methanol. The filtrate was evaporated and the residue chromatographed on silica gel, eluting with dichloromethane/methanol/0.88 ammonia (89:11:1.1) to give product (133 mg, 87%).

Workup

  1. customevaporated to dryness
  2. additionA part solution/part suspension of this material in dichloromethane (8.5 ml)
  3. additionmethanol (1.5 ml) was treated with MP-carbonate resin (obtained from Argonaut Technologies) (1.2 g)
  4. stirringstirred for 3 h
  5. filtrationfiltered
  6. washthe resin washed well with 1:1 dichloromethane/methanol
  7. customThe filtrate was evaporated
  8. customthe residue chromatographed on silica gel
  9. washeluting with dichloromethane/methanol/0.88 ammonia (89:11:1.1)

Sources & evidence

ORD record
ord-aa521d6d0eb6459d8131436e8342f518
Source dataset
uspto-grants-2010_06
Patent number
US07732461B2

Reaction notes

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