4-Methylmorpholine → HCID 67089638, compound

HRID 2075477Notes

Reaction equation

HRID 2075477 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](/[CH:10]=[CH:11]/[C:12]2[CH:20]=[CH:19][C:15]([C:16]([OH:18])=O)=[CH:14][CH:13]=2)=[N:2]1.C(OC(=O)[NH:27][C@H:28]1[CH2:32][CH2:31][NH:30][CH2:29]1)(C)(C)C.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CN1CCOCC1.Cl.CO>CO>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](/[CH:10]=[CH:11]/[C:12]2[CH:13]=[CH:14][C:15]([C:16]([N:30]3[CH2:31][CH2:32][C@H:28]([NH2:27])[CH2:29]3)=[O:18])=[CH:19][CH:20]=2)=[N:2]1

Participants

8

Reactant 6

HCID 79724-MethylmorpholineHCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 11437002(E)-4-(2-(1H-indazol-3-yl)vinyl)benzoic acidHCID 21893726Hydrochloride methanol

Product 1

HCID 67089638HCID 67089638, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

The product obtained using (E)-4-[2-(1H-indazol-3-yl)vinyl]benzoic acid (700 mg, 2.65 mmol) obtained in Step 6 of Example 1, (S)-(pyrrolidin-3-yl)carbamic acid tert-butyl ester (740 g, 3.98 mmol), 1-hydroxybenzotriazole monohydrate (470 mg, 3.46 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (710 mg, 3.72 mmol) and N-methylmorpholine (0.608 mL, 5.32 mmol) in a similar manner to Example 5, was dissolved in methanol (1.5 mL) and the solution was added with 4 mol/L hydrogen chloride-methanol solution (1.50 mL), followed by heating under reflux at 60° C. for 60 minutes. The reaction mixture was concentrated under reduced pressure, and the residue was added with saturated aqueous sodium hydrogencarbonate solution and ethyl acetate, followed by extraction. The crude product was crystallized from acetone to obtain Compound 159 (190 mg, 22%).

Workup

  1. customThe product obtained
  2. temperatureby heating
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionthe residue was added with saturated aqueous sodium hydrogencarbonate solution and ethyl acetate
  5. extractionfollowed by extraction
  6. customThe crude product was crystallized from acetone

Sources & evidence

ORD record
ord-183980387c96464a8ee5adb929a8e4e6
Source dataset
uspto-grants-2011_04
Patent number
US07919517B2

Reaction notes

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