Cyclopropanemethanamine → N-(Cyclopropylmethyl)-2-methyl-4-(1-pyrrolidinyl)-7-quinolinamine

HRID 2121634Notes

Reaction equation

HRID 2121634 reaction equation
I[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)=[CH:7][C:8]([CH3:12])=[N:9]2)=[CH:4][CH:3]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.[NH2:64][CH2:65][CH:66]1[CH2:68][CH2:67]1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:66]1([CH2:65][NH:64][C:2]2[CH:11]=[C:10]3[C:5]([C:6]([N:13]4[CH2:17][CH2:16][CH2:15][CH2:14]4)=[CH:7][C:8]([CH3:12])=[N:9]3)=[CH:4][CH:3]=2)[CH2:68][CH2:67]1

Participants

6

Reactant 3

HCID 75646CyclopropanemethanamineHCID 634876Binap, (A+-)-HCID 113366637-Iodo-2-methyl-4-pyrrolidin-1-yl-quinoline

Product 1

HCID 23433902N-(Cyclopropylmethyl)-2-methyl-4-(1-pyrrolidinyl)-7-quinolinamineYield 30%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

A suspension of 1.01 g (3 mmol) of 7-iodo-2-methyl-4-pyrrolidin-1-yl-quinoline, 0.186 g (0.3 mmol) rac BINAP, 33.7 mg (0.15 mmol) of palladium(II)acetate and 0.87 g (9 mmol) of sodium tert-butylate in toluene (25 ml) was treated at RT with 0.427 g (6 mmol) of aminomethyl cyclopropane and then heated to reflux under an argon atmosphere for 20 h. The reaction mixture was then filterd by suction over fiberglass filter paper and the filtrate was partitioned between EtOAc and water. The layers were separated, the organic layer dried over sodium sulphate and concentrated in vacuo. The residue was applied to silica gel column with CH2Cl2/MeOH/NH4OH (15:1:0.2) as eluent. Combination of the purified fractions and concentration in vacuo gave 253 mg (30%) of the desired cyclopropylmethyl-(2-methyl-4-pyrrolidin-1-yl-quinolin-7-yl)-amine as light yellow foam. ISP mass spectrum, m/e: 282.2 (M+1 calculated for C18H23N3O: 282).

Workup

  1. temperatureheated
  2. temperatureto reflux under an argon atmosphere for 20 h
  3. filtrationfilter paper
  4. customthe filtrate was partitioned between EtOAc and water
  5. customThe layers were separated
  6. dry with materialthe organic layer dried over sodium sulphate
  7. concentrationconcentrated in vacuo
  8. concentrationCombination of the purified fractions and concentration in vacuo

Sources & evidence

ORD record
ord-49027f9b1801457c8e23e3a27c3ba388
Source dataset
uspto-grants-2004_02
Patent number
US06696467B2

Reaction notes

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