N,N-Dimethylglycine → HCID 68986610, compound

HRID 1752572Notes

Reaction equation

HRID 1752572 reaction equation
[CH3:1][N:2]([CH3:7])[CH2:3][C:4](O)=[O:5].C(Cl)(=O)C(Cl)=O.C(OC([N:21]1[C:29]2[C:24](=[CH:25][C:26]([C:30]3[CH:31]=[N:32][N:33]([CH2:35][C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[CH:34]=3)=[CH:27][CH:28]=2)[C:23]([NH2:42])=[N:22]1)=O)(C)(C)C.C(=O)([O-])[O-].[K+].[K+].FC(F)(F)C(O)=O>ClCCl.CN(C)C=O.O1CCCC1>[CH2:35]([N:33]1[CH:34]=[C:30]([C:26]2[CH:25]=[C:24]3[C:29](=[CH:28][CH:27]=2)[NH:21][N:22]=[C:23]3[NH:42][C:4](=[O:5])[CH2:3][N:2]([CH3:7])[CH3:1])[CH:31]=[N:32]1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

9

Reactant 5

HCID 673N,N-DimethylglycineHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 65578Oxalyl chlorideHCID 68738629HCID 68738629, compound

Product 1

HCID 68986610HCID 68986610, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 2-(dimethylamino)acetic acid (32 mg, 0.308 mmol) and oxalyl chloride (0.31 mL, 0.61 mmol) in dichloromethane (5 mL) and dimethylformamide (2 drops) was stirred at ambient temperature for about 1 hour then concentrated under reduced pressure. The residue was suspended in tetrahydrofuran (3 mL) and added to a suspension of Example 303A (40 mg, 0.103 mmol) and potassium carbonate (43 mg, 0.308 mmol) in tetrahydrofuran (5 mL). The reaction mixture was stirred at ambient temperature for about 30 minutes then trifluoroacetic acid (4 mL) was added and the reaction mixture was heated at about 60° C. for about 20 hours. The reaction mixture was cooled to ambient temperature and concentrated under reduced pressure, diluted with dichloromethane (20 mL) and washed with 15% aqueous sodium hydroxide solution (20 mL). The organic extract was separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by reverse-phase HPLC using acetonitrile/water (0.05 M ammonium acetate) gradient elution method to afford the title compound as the acetate salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.97 (s, 1H), 8.21 (s, 1H), 7.83 (s, 1H), 7.82 (s, 1H), 7.56 (d, J=8.7 Hz, 1H), 7.43 (d, J=8.6 Hz, 1H), 7.32-7.40 (m, 2H), 7.25-7.32 (m, 3H), 5.35 (s, 2H), 3.16 (s, 2H), 2.33 (s, 6H), 1.91 (s, 3H). MS (ESI+) m/z 375 (M+H)+.

Workup

  1. concentrationthen concentrated under reduced pressure
  2. stirringThe reaction mixture was stirred at ambient temperature for about 30 minutes
  3. temperaturethe reaction mixture was heated at about 60° C. for about 20 hours
  4. temperatureThe reaction mixture was cooled to ambient temperature
  5. concentrationconcentrated under reduced pressure
  6. additiondiluted with dichloromethane (20 mL)
  7. washwashed with 15% aqueous sodium hydroxide solution (20 mL)
  8. extractionThe organic extract
  9. customwas separated
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe crude material was purified by reverse-phase
  14. washacetonitrile/water (0.05 M ammonium acetate) gradient elution method

Sources & evidence

ORD record
ord-b18a473d2ecd4ee5916eb9d74b2c6ebc
Source dataset
uspto-grants-2015_10
Patent number
US09163007B2

Reaction notes

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