Trifluoroacetic acid → HCID 22632328, compound

HRID 2417543Notes

Reaction equation

HRID 2417543 reaction equation
[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:14][C:13]3[CH:15]=[CH:16][CH:17]=[CH:18][C:12]=3[N:11]([CH2:19][C:20]#[CH:21])[C:10](=[O:22])[CH2:9]2)=[O:7])=[CH:4][CH:3]=1.I[C:26]1[CH:27]=[N:28][CH:29]=[CH:30][C:31]=1[NH:32]C(=O)OC(C)(C)C.C(N(CC)CC)C.C1CCN2C(=NCCC2)CC1.[F:58][C:59]([F:64])([F:63])[C:60]([OH:62])=[O:61]>CN(C=O)C.ClCCl.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu](I)I.C(OCC)(=O)C>[F:58][C:59]([F:64])([F:63])[C:60]([OH:62])=[O:61].[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[CH2:14][C:13]3[CH:15]=[CH:16][CH:17]=[CH:18][C:12]=3[N:11]([CH2:19][C:20]3[NH:32][C:31]4[CH:30]=[CH:29][N:28]=[CH:27][C:26]=4[CH:21]=3)[C:10](=[O:22])[CH2:9]2)=[O:7])=[CH:4][CH:3]=1

Participants

11

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 10903275(3-Iodo-pyridin-4-yl)-carbamic acid tert-butyl esterHCID 22632670HCID 22632670, compound

Product 1

HCID 22632328HCID 22632328, compound

Reagents, catalysts & solvents 5

HCID 83717Copper iodideCatalystHCID 178419050HCID 178419050, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

57 mg (0.13 mmol) of 4-(4-chlorobenzoyl)-1-(2-propynyl)-1,3,4,5-tetrahydrobenzo[e][1,4]diazepin-2-on obtained in step 1 and 50 mg (0.16 mmol) of t-butyl (3-iodopyridin-4-yl)carbamate were dissolved in 5 ml of DMF. 5.6 mg (0.08 mmol) of bis(triphenylphosphine)palladium (II), 1 mg (0.005 mmol) of copper iodide and 0.09 ml (0.64 mmol) of triethylamine were added to the obtained solution, and they were stirred at 100° C. for 1-5 hours. The reaction solution was cooled to 50° C. 0.05 ml (0.32 mmol) of DBU was added thereto, and they were stirred at 50° C. for 30 minutes and then at room temperature overnight. After the treatment with ethyl acetate as the extracting solvent by an ordinary method, the obtained crude product was dissolved in 10 ml of dichloromethane. 1.5 ml of trifluoroacetic acid was added to the obtained solution, and they were stirred overnight. The solvent was evaporated, and the obtained crude product was treated in the same manner as in step 3 in Example 1 to obtain the title compound.

Workup

  1. temperatureThe reaction solution was cooled to 50° C
  2. stirringthey were stirred at 50° C. for 30 minutes
  3. customat room temperature
  4. customovernight
  5. stirringwere stirred overnight
  6. customThe solvent was evaporated
  7. customthe obtained crude product
  8. additionwas treated in the same manner as in step 3 in Example 1

Sources & evidence

ORD record
ord-923f9d35f028430a80bd8dfd0ae68b5c
Source dataset
uspto-grants-2004_11
Patent number
US06825191B2

Reaction notes

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