Diisopropylethylamine → HCID 178422074, compound

HRID 1773910Notes

Reaction equation

HRID 1773910 reaction equation
[CH3:1][C:2]1[N:11]2[C:5]([CH:6]([O:16][CH:17]3[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]3)[C:7]3[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=3[CH2:9][CH2:10]2)=[N:4][C:3]=1[C:24]1[CH:29]=[CH:28][C:27]([S:30][CH2:31][CH2:32][NH2:33])=[CH:26][CH:25]=1.C(OC([NH:41][C:42](N1C=CC=N1)=[N:43]C(OC(C)(C)C)=O)=O)(C)(C)C.CCN(C(C)C)C(C)C>C(#N)C.O.CCOC(C)=O>[CH3:1][C:2]1[N:11]2[C:5]([CH:6]([O:16][CH:17]3[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]3)[C:7]3[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=3[CH2:9][CH2:10]2)=[N:4][C:3]=1[C:24]1[CH:29]=[CH:28][C:27]([S:30][CH2:31][CH2:32][NH:33][C:42]([NH2:43])=[NH:41])=[CH:26][CH:25]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 4428040N,N'-Bis(tert-butoxycarbonyl)-1H-pyrazole-1-carboxamidineHCID 86703989HCID 86703989, compound

Product 1

HCID 178422074HCID 178422074, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2-{4-[1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenylsulfanyl}-ethylamine (example 161) (170 mg, 0.368 mmole) in ACN (5 mL) are added N,N′-bis(tert-butoxycarbonyl)-1H-pyrazole-1-carboxamidine) (125 mg, 0.405 mmole) and DIEA (80 μL, 0.423 mmole). The reaction mixture is heated at 50° C. for 24 hours, then it is diluted with water and AcOEt. The organic phase is dried over MgSO4, filtered and the solvent is removed under reduced pressure. The residue is dissolved in CH2Cl2 (2 mL) and TFA is added (2 mL). The reaction mixture is stirred at room temperature for 3 hours. The reaction mixture is diluted with water, then 10N NaOH is added dropwise until pH 10 is reached. The aqueous phase is extracted three times with CH2Cl2. The organic phase dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is purified by silica gel chromatography using (CH2Cl2:MeOH:NH4OH) (90:1:0.1) to (8:2:0.2) to give N-(2-{4-[1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenylsulfanyl}-ethyl)-guanidine.

Workup

  1. dry with materialThe organic phase is dried over MgSO4
  2. filtrationfiltered
  3. customthe solvent is removed under reduced pressure
  4. dissolutionThe residue is dissolved in CH2Cl2 (2 mL)
  5. additionTFA is added (2 mL)
  6. additionThe reaction mixture is diluted with water
  7. addition10N NaOH is added dropwise until pH 10
  8. extractionThe aqueous phase is extracted three times with CH2Cl2
  9. dry with materialThe organic phase dried over magnesium sulphate
  10. filtrationfiltered
  11. customthe solvent is removed under reduced pressure
  12. customThe residue is purified by silica gel chromatography

Sources & evidence

ORD record
ord-0da1b3bb053a42db90136fcfcb033b70
Source dataset
uspto-grants-2016_02
Patent number
US09255101B2

Reaction notes

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