Hydrochloric Acid → HCID 44194488, compound

HRID 1697467Notes

Reaction equation

HRID 1697467 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[O:9][CH2:8][C:7]([C:13]([NH:15][CH:16]([C:18]1[CH:19]=[C:20]3[C:24](=[CH:25][CH:26]=1)[N:23](C1CCCCO1)[N:22]=[CH:21]3)[CH3:17])=[O:14])=[CH:6]2.CO>>[NH:23]1[C:24]2[C:20](=[CH:19][C:18]([CH:16]([NH:15][C:13]([C:7]3[CH2:8][O:9][C:10]4[C:5]([CH:6]=3)=[CH:4][C:3]([Cl:2])=[CH:12][CH:11]=4)=[O:14])[CH3:17])=[CH:26][CH:25]=2)[CH:21]=[N:22]1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 66945597HCID 66945597, compound

Product 1

HCID 44194488HCID 44194488, compoundYield 24.7%

Conditions

Temperature
50 °C

Procedure

Concentrated hydrochloric acid (1 mL) was added to a stirred solution of 6-chloro-N-(1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)ethyl)-2H-chromene-3-carboxamide (178 mg, 0.4 mmol) in methanol (5 mL, 0.1 mol) at room temperature. The mixture was heated to 50° C. and stirred for 1 hour. TLC indicated complete reaction, so after allowing to cool, the mixture was concentrated under vacuum and the residue partitioned between sat'd NaHCO3 (30 mL—care: initial evolution of gas as reaction with excess acid ensues) and EtOAc (50 mL). The organic layer was washed with brine (1×20 mL), dried (MgSO4), filtered and the solvent removed under vacuum to leave a crude solid. The solid was triturated with EtOAc (10 mL) and filtered. The filter cake was washed with EtOAc (2×3 mL) to give the product (35 mg). m/z=354.3 (M+1)+. 1H NMR (400 MHz; DMSO-d6) δ 13.00 (s, 1H), 8.64 (d, J=8.0 Hz, 1H), 8.04 (s, 1H), 7.70 (s, 1H), 7.48 (d, J=8.0 Hz, 1H), 7.39 (m, 1H), 7.32-7.24 (m, 3H), 6.86 (d, J=8.4 Hz, 1H), 5.21-5.13 (m, 1H), 4.97-4.88 (m, 2H), 1.48 (d, J=7.0 Hz, 3H).

Workup

  1. customreaction
  2. temperatureto cool
  3. concentrationthe mixture was concentrated under vacuum
  4. customthe residue partitioned between sat'd NaHCO3 (30 mL—care
  5. custominitial evolution of gas as reaction with excess acid ensues) and EtOAc (50 mL)
  6. washThe organic layer was washed with brine (1×20 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customthe solvent removed under vacuum
  10. customto leave a crude solid
  11. customThe solid was triturated with EtOAc (10 mL)
  12. filtrationfiltered
  13. washThe filter cake was washed with EtOAc (2×3 mL)

Sources & evidence

ORD record
ord-158c39b5c09b4bd99ee5e8b41e27cd71
Source dataset
uspto-grants-2012_04
Patent number
US08163901B2

Reaction notes

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