Potassium Hydroxide → HCID 86700211, compound

HRID 879404Notes

Reaction equation

HRID 879404 reaction equation
Cl.Cl.[N:3]1[C:12]2[CH2:11][CH2:10][NH:9][CH2:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.[OH-].[K+].Br[C:16]1[S:17][C:18]2[C:24]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)=[C:23]([C@H:32]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])[C:33]([O:35]CC)=[O:34])[C:22]([CH3:43])=[CH:21][C:19]=2[N:20]=1.[OH-].[Na+]>CCO.C1COCC1.CN(C)C(=O)C.O.C(Cl)Cl>[C:39]([O:38][C@@H:32]([C:23]1[C:22]([CH3:43])=[CH:21][C:19]2[N:20]=[C:16]([N:9]3[CH2:10][CH2:11][C:12]4[N:3]=[CH:4][CH:5]=[CH:6][C:7]=4[CH2:8]3)[S:17][C:18]=2[C:24]=1[C:25]1[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=1)[C:33]([OH:35])=[O:34])([CH3:42])([CH3:40])[CH3:41]

Participants

10

Reactant 4

HCID 14797Potassium HydroxideHCID 14798Sodium HydroxideHCID 224808525,6,7,8-Tetrahydro-1,6-naphthyridine--hydrogen chloride (1/2)HCID 86700141(S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate

Product 1

HCID 86700211HCID 86700211, compound

Reagents, catalysts & solvents 5

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

A vial was charged with 5,6,7,8-tetrahydro-1,6-naphthyridine, dihydrochloride, hydrate (125 mg), DCM (1.5 mL), and 50% w/v aq KOH (200 μL). The vial was shaken. Then H2O (1.3 mL) was added. The organic phase was collected, dried with a small amount of Na2SO4, decanted, and concentrated to give the free base. N,N-dimethylacetamide (500 μL), and (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (25 mg, 50 μmol) were added. The vessel was sealed and heated to 100° C. for 30 min. Then THF (1 mL), EtOH (absolute, 500 μL), and 5 M aq NaOH (500 μL) were added. The reaction was heated to 100° C. for 30 min. The reaction was cooled to 23° C., and filtered (0.45 micron teflon syringe filter). The filtrate was purified by reverse phase HPLC, eluting by 5-100% acetonitrile in H2O with 0.1% TFA to give the desired product. LCMS-ESI+: calc'd for C28H28ClN3O3S: 522.2, 524.2 (M+H+); Found: 522.3, 524.2 (M+H+). NMR (400 MHz, CD3OD): δ 8.62 (d, J=5.6 Hz, 1H), 8.29 (d, J=8.1 Hz, 1H), 7.78 (dd, J=7.9, 5.6 Hz, 1H), 7.63 (dd, J=8.5, 1.9 Hz, 1H), 7.58-7.52 (m, 2H), 7.52-7.44 (m, 1H), 7.38 (app. s, 1H), 5.15 (s, 1H), 4.96 (s, broad, 2H), 4.03 (t, J=5.9 Hz, 2H), 3.31-3.23 (m, 2H), 2.51 (s, 3H), 0.95 (s, 9H).

Workup

  1. customThe organic phase was collected
  2. dry with materialdried with a small amount of Na2SO4
  3. customdecanted
  4. concentrationconcentrated
  5. customto give the free base
  6. customThe vessel was sealed
  7. temperatureThe reaction was heated to 100° C. for 30 min
  8. temperatureThe reaction was cooled to 23° C.
  9. filtrationfiltered
  10. filtration(0.45 micron teflon syringe filter)
  11. customThe filtrate was purified by reverse phase HPLC
  12. washeluting by 5-100% acetonitrile in H2O with 0.1% TFA

Sources & evidence

ORD record
ord-7c7c32f994ae40ebb352964da2b8502d
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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