Diisopropylcarbodiimide → HCID 59618717, compound

HRID 1691458Notes

Reaction equation

HRID 1691458 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([N:14]2[C:20]3[CH:21]=[C:22]([C:25]([OH:27])=O)[CH:23]=[CH:24][C:19]=3[NH:18][C:17]3[N:28]=[C:29]([C:32]([F:35])([F:34])[F:33])[CH:30]=[CH:31][C:16]=3[CH2:15]2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[C:36](=[N:39]O)([NH2:38])[CH3:37].CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CC(C)N=C=NC(C)C>C(Cl)Cl.CN(C=O)C>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([N:14]2[C:20]3[CH:21]=[C:22]([C:25]4[O:27][N:39]=[C:36]([CH3:37])[N:38]=4)[CH:23]=[CH:24][C:19]=3[NH:18][C:17]3[N:28]=[C:29]([C:32]([F:34])([F:33])[F:35])[CH:30]=[CH:31][C:16]=3[CH2:15]2)(=[O:12])=[O:13])=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 12734DiisopropylcarbodiimideHCID 30926N-HydroxyacetamidineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66901628HCID 66901628, compound2×

Product 1

HCID 59618717HCID 59618717, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 6-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine-8-carboxylic acid (intermediate 58, 60 mg, 0.119 mmol), acetamide oxime (10 mg, 0.141 mmol), DIPEA (18 mg, 0.141 mmol), HOBt (19 mg, 0.14 mmol), DIC (23 mg, 0.18 mmol) in DCM (0.4 mL) and DMF (0.1 mL) was stirred at rt for 3 h. The reaction was quenched with water and the product was extracted with EtOAc. The combined extracts were washed with 5% NaHCO3, brine, dried (MgSO4) and concentrated. The residue was dissolved in NMP and was heated in a microwave reactor at 120° C. for 1 h. The reaction was quenched with water and the product was extracted with EtOAc. The extracts were washed with water and brine, dried (MgSO4) and concentrated. Flash column purification of the residue on SiO2 afforded the title compound. LC/MS: m/e 544.1 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 8.38 (1H, d, J=1.6 Hz), 8.00 (1H, dd, J=8.4, 1.8 Hz), 7.63 (1H, d, J=7.4 Hz), 7.16 (1H, d, J=7.4 Hz), 7.13 (1H, d, J=8.4 Hz), 7.05 (1H, br s), 6.97 (2H, J=8.5 Hz), 6.90 (1H, d, J=8.4 Hz), 4.65-4.95 (2H, br), 2.51 (3H, s), 1.26 (9H, s).

Workup

  1. customThe reaction was quenched with water
  2. extractionthe product was extracted with EtOAc
  3. washThe combined extracts were washed with 5% NaHCO3, brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in NMP
  7. temperaturewas heated in a microwave reactor at 120° C. for 1 h
  8. customThe reaction was quenched with water
  9. extractionthe product was extracted with EtOAc
  10. washThe extracts were washed with water and brine
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated
  13. customFlash column purification of the residue on SiO2

Sources & evidence

ORD record
ord-580ac44eeea742888063e8ea32d99fe7
Source dataset
uspto-grants-2012_04
Patent number
US08153626B2

Reaction notes

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