Diisopropylethylamine → HCID 178512992, compound

HRID 495136Notes

Reaction equation

HRID 495136 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[Cl:8][C:9]1[CH:10]=[CH:11][C:12]2[O:17][C:16](=[O:18])[CH:15]=[C:14]([O:19]CCCNC)[C:13]=2[CH:25]=1.C(N(C(C)C)CC)(C)C.C(OC([NH:42][C:43]([N:52]1[CH:56]=[CH:55][CH:54]=N1)=[N:44]C(OC(C)(C)C)=O)=O)(C)(C)C>C(Cl)Cl>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[Cl:8][C:9]1[CH:10]=[CH:11][C:12]2[O:17][C:16](=[O:18])[CH:15]=[C:14]([O:19][CH2:54][CH2:55][CH2:56][NH:52][C:43]([NH2:42])=[NH:44])[C:13]=2[CH:25]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 4428040N,N'-Bis(tert-butoxycarbonyl)-1H-pyrazole-1-carboxamidineHCID 86596924HCID 86596924, compound

Product 1

HCID 178512992HCID 178512992, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

6-Chloro-4-(3-methylamino-propoxy)-1-benzopyran-2-one trifluoroacetic acid salt (200 mg, 0.543 mmol) is suspended in 7 mL of DCM. Diisopropylethylamine is added dropwise until pH=9 by pH paper. N,N′-Bis(tert-butoxycarbonyl)-1-H-pyrazole-1-carboxamidine (169 mg, 0.543 mmol) is added and is stirred at ambient temperature overnight. The reaction mixture is concentrated in vacuo and Et2O is added to form a white precipitate, which is filtered and is washed with Et2O. The crude material is treated with neat TFA (10 mL) for 30 min at ambient temperature. The TFA is removed under reduced pressure. Et2O is added to precipitate the product, which is filtered, is washed with Et2O, and is dried. The crude material is further purified by reversed-phase HPLC to afford the title compound as the trifluoroacetic acid salt. (108 mg, 48.6%). %). 1H NMR (DMSO-d6, 300 MHz) δ 7.86 (1H, d, J=2.5 Hz), 7.72 (1H, dd, J=2.5, 8.75 Hz), 7.64 (1H, t, J=5.5 Hz), 7.47 (1H, d, J=8.75 Hz), 7.12 (3H, br s), 6.00 (1H, s), 4.26 (2H, t, J=5.75 Hz), 3.36 (2H, m, J=6.25 Hz), 2.04 (2H, m, J=6.25 Hz); MS (ESI, Pos.) calcd for C13H14ClN3O3 m/z [M+H]=296.1, found 296.0.

Workup

  1. concentrationThe reaction mixture is concentrated in vacuo and Et2O
  2. additionis added
  3. customto form a white precipitate, which
  4. filtrationis filtered
  5. washis washed with Et2O
  6. additionThe crude material is treated with neat TFA (10 mL) for 30 min at ambient temperature
  7. customThe TFA is removed under reduced pressure
  8. additionEt2O is added
  9. customto precipitate the product, which
  10. filtrationis filtered
  11. washis washed with Et2O
  12. customis dried
  13. customThe crude material is further purified by reversed-phase HPLC

Sources & evidence

ORD record
ord-142234e9ea344453834f16140df7ac1d
Source dataset
uspto-grants-2009_05
Patent number
US07538233B2

Reaction notes

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