Diisopropylethylamine → HCID 70817761, compound

HRID 1501322Notes

Reaction equation

HRID 1501322 reaction equation
Br[CH:2]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14][CH2:13][CH2:12]2)=[CH:7][CH:6]=1)=O.[NH2:29][C:30]1[N:35]=[N:34][C:33]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:32][CH:31]=1.C(N(CC)C(C)C)(C)C>C(O)(C)C>[C:18]([O:17][C:16]([NH:15][C:11]1([C:8]2[CH:7]=[CH:6][C:5]([C:3]3[N:29]=[C:30]4[CH:31]=[CH:32][C:33]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[N:34][N:35]4[C:2]=3[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)=[CH:10][CH:9]=2)[CH2:12][CH2:13][CH2:14]1)=[O:22])([CH3:20])([CH3:19])[CH3:21]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 25067380Ethyl 6-aminopyridazine-3-carboxylateHCID 86691038tert-Butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate

Product 1

HCID 70817761HCID 70817761, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of crude tert-butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate that was prepared in a manner analgous to that described for Intermediate Example Int-1-A (3.3 g, ˜80% purity, 5.79 mmol), ethyl 6-aminopyridazine-3-carboxylate (CAS-Nr. 98548-01-7, 1 g, 5.57 mmol), N,N-diisopropylethylamine (0.97 mL, 5.57 mmol) and activated 3 Å molecular sieves in isopropanol (30.4 mL) was heated for 20 hours under reflux. On cooling the mixture was partitioned between DCM and water, stirred vigorously and filtered through a silicone coated filter paper. The filtrate was concentrated in vacuo, taken up in DCM and washed with dilute aqueous hydrochloric acid (1N) and brine, dried and concentrated in vacuo to give the crude title compound. Purification was achieved by chromatography on silica (gradient elution: Hexane:EtOAc 9:1 to Hexane:EtOAc 1:1) to give the title compound (2.80 g, 92% purity, 90% yield).

Workup

  1. customwas prepared in a manner analgous to
  2. temperaturewas heated for 20 hours
  3. temperatureunder reflux
  4. temperatureOn cooling the mixture
  5. customwas partitioned between DCM and water
  6. filtrationfiltered through a silicone coated filter paper
  7. concentrationThe filtrate was concentrated in vacuo
  8. washwashed with dilute aqueous hydrochloric acid (1N) and brine
  9. customdried
  10. concentrationconcentrated in vacuo
  11. customto give the crude title compound
  12. customPurification

Sources & evidence

ORD record
ord-d118f2e3f44d4ecaa3f42278dbcf545c
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

Loading…