Morpholine → Ethyl 3-{[(benzyloxy)carbonyl]amino}-7-morpholin-4-ylquinoline-2-carboxylate

HRID 924440Notes

Reaction equation

HRID 924440 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[C:17](Br)[CH:16]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(O)(C)(C)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[C:17]([N:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1)[CH:16]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 62657Potassium Phosphate, TribasicHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 86726857Ethyl 3-(((benzyloxy)carbonyl)amino)-7-bromoquinoline-2-carboxylate

Product 1

HCID 86726891Ethyl 3-{[(benzyloxy)carbonyl]amino}-7-morpholin-4-ylquinoline-2-carboxylateYield 98.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6386tert-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl 3-{[(benzyloxy)carbonyl]amino}-7-bromoquinoline-2-carboxylate (300 mg, 0.7 mmol), morpholine (120 mg, 1.4 mmol), Pd(OAc)2 (20 mg), dicyclohexyl(2′,6′-diisopropoxybiphenyl-2-yl)phosphine (49 mg, 0.10 mmol), and K3PO4 (580 mg, 2.8 mmol) in tert-butanol (10 mL) in a sealed vial was purged with nitrogen then heated at 100° C. for 1 h. The solution was allowed to cool then and diluted with EtOAc, and the mixture was filtered through diatomaceous earth. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by flash chromatography on 40 g of silica gel, eluting with 0-100% EtOAc in hexanes, to give the sub-title compound (0.3 g, 20%). LCMS (ESI) calc. for C24H26N3O5 [M+H]+: m/z=436.2. found: 436.1.

Workup

  1. customvial was purged with nitrogen
  2. temperatureto cool
  3. additiondiluted with EtOAc
  4. filtrationthe mixture was filtered through diatomaceous earth
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by flash chromatography on 40 g of silica gel
  7. washeluting with 0-100% EtOAc in hexanes

Sources & evidence

ORD record
ord-f885fa28c73849769ef52659a9a22e9a
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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