Cyclopropanemethanamine → N-(Cyclopropylmethyl)-2-methyl-4-(pyrrolidin-1-yl)quinazolin-7-amine

HRID 1271215Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1271215
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)=[N: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)=[N:7][C:8]([CH3:12])=[N:9]3)=[CH:4][CH:3]=2)[CH2:68][CH2:67]1

Komponenten

6

Edukt 3

HCID 75646CyclopropanemethanamineHCID 634876Binap, (A+-)-HCID 224749397-Bromo-2-methyl-4-pyrrolidin-1-yl-quinazoline

Produkt 1

HCID 18452841N-(Cyclopropylmethyl)-2-methyl-4-(pyrrolidin-1-yl)quinazolin-7-amineAusbeute 46,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittel

Versuchsvorschrift

A suspension of 0.15 g (0.513 mmol) of 7-bromo-2-methyl-4-pyrrolidin-1-yl-quinazoline, 21.3 mg (0.034 mmol) racemic BINAP, 3.8 mg (0.017 mmol) of palladium(II)acetate and 65.8 mg (0.685 mmol) of sodium tert-butylate in toluene (8 ml) was treated at RT with 0.365 g (5.13 mmol) of aminomethyl cyclopropane and then heated to reflux under an argon atmosphere for 20 h. The reaction mixture was then filtered 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 (10:1:0.2) as eluent. Combination of the purified fractions and concentration in vacuo gave 68 mg (46.9%) of the desired cyclopropylmethyl-(2-methyl-4-pyrrolidin-1-yl-quinazolin-7-yl)-amine as brown viscous oil. ISP mass spectrum, m/e: 283.2 (M+1 calculated for C17H22N4: 283).

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-266dec4850b441988707391e3c0936f3
Quelldatensatz
uspto-grants-2007_04
Patentnummer
US07205309B2

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