HCID 86711139, compound → HCID 136633865, compound

HRID 1472628Notes

Reaction equation

HRID 1472628 reaction equation
[Si]([O:8][CH:9]1[C:14]2=[N:15][C:16]([CH3:48])=[C:17]([CH2:20][CH2:21][N:22]3[CH2:27][CH2:26][CH:25]([C:28]4[C:32]5[CH:33]=[CH:34][C:35]([O:37][CH2:38][CH2:39][NH:40]C(=O)OC(C)(C)C)=[CH:36][C:31]=5[O:30][N:29]=4)[CH2:24][CH2:23]3)[C:18](=[O:19])[N:13]2[CH2:12][CH2:11][CH2:10]1)(C(C)(C)C)(C)C>Cl.C(O)(C)C>[NH2:40][CH2:39][CH2:38][O:37][C:35]1[CH:34]=[CH:33][C:32]2[C:28]([CH:25]3[CH2:24][CH2:23][N:22]([CH2:21][CH2:20][C:17]4[C:18](=[O:19])[N:13]5[CH2:12][CH2:11][CH2:10][CH:9]([OH:8])[C:14]5=[N:15][C:16]=4[CH3:48])[CH2:27][CH2:26]3)=[N:29][O:30][C:31]=2[CH:36]=1.[OH:8][CH:9]1[C:14]2=[N:15][C:16]([CH3:48])=[C:17]([CH2:20][CH2:21][N:22]3[CH2:27][CH2:26][CH:25]([C:28]4[C:32]5[CH:33]=[CH:34][C:35]([OH:37])=[CH:36][C:31]=5[O:30][N:29]=4)[CH2:24][CH2:23]3)[C:18](=[O:19])[N:13]2[CH2:12][CH2:11][CH2:10]1

Participants

4

Reactant 1

HCID 86711139HCID 86711139, compound

Product 2

HCID 73331224HCID 73331224, compoundHCID 136633865HCID 136633865, compoundYield 5%

Reagents, catalysts & solvents 1

HCID 21912024Isopropanol hydrochlorideSolvent

Conditions

Temperature
60 °C

Procedure

A solution of tert-butyl (2-((3-(1-(2-(9-((tert-butyldimethylsilyl)oxy)-2-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-3-yl)ethyl)piperidin-4-yl)benzo[d]isoxazol-6-yl)oxy)ethyl)carbamate, prepared as described in the previous step, (70 mg, 0.103 mmol) in HCl/isopropanol (10 mL, 5 N) was stirred for 1 h at 60° C. The reaction mixture was evaporated at 40° C. under reduced pressure and dissolved carefully in aqueous saturated sodium bicarbonate solution (5 mL) and extracted with dichloromethane (3×10 mL). The combined organic layers were dried over Na2SO4, filtered, and evaporated under reduced pressure at 40° C. The aqueous layer still contained product, which was recovered by evaporating the aqueous layer to dryness at 40° C. under reduced pressure. The resulting residue from the aqueous layer was re-dissolved in water and brought over a conditioned Waters Oasis SPE (6 cc) column and afterwards eluted with methanol. The methanol elution fraction was combined with the residue of the dichloromethane extraction and evaporated to dryness at 40° C. under reduced pressure to yield the title compound along with a side product (ESI-MS (M+1) 468; side product being 5% 9-hydroxy-3-(2-(4-(6-hydroxybenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (M+1) 425). The mixture was used in the next step without additional purification.

Workup

  1. customThe reaction mixture was evaporated at 40° C. under reduced pressure
  2. dissolutiondissolved carefully in aqueous saturated sodium bicarbonate solution (5 mL)
  3. extractionextracted with dichloromethane (3×10 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure at 40° C
  7. customThe aqueous layer still contained product, which was recovered
  8. customby evaporating the aqueous layer to dryness at 40° C. under reduced pressure
  9. dissolutionThe resulting residue from the aqueous layer was re-dissolved in water
  10. washafterwards eluted with methanol
  11. washThe methanol elution fraction
  12. extractionwas combined with the residue of the dichloromethane extraction
  13. customevaporated to dryness at 40° C. under reduced pressure

Sources & evidence

ORD record
ord-9013397cd0f0452f939af694f34a7513
Source dataset
uspto-grants-2015_04
Patent number
US09012648B2

Reaction notes

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