Prolinol, (R)- → HCID 68880437, compound

HRID 1785179Notes

Reaction equation

HRID 1785179 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH2:13][O:14][CH3:15])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:29][CH2:30][CH2:31][CH2:32]Cl)=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1.[NH:34]1[CH2:38][CH2:37][CH2:36][C@@H:35]1[CH2:39][OH:40]>COCCO.ClCCl>[Cl:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH2:13][O:14][CH3:15])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:29][CH2:30][CH2:31][CH2:32][N:34]3[CH2:38][CH2:37][CH2:36][C@@H:35]3[CH2:39][OH:40])=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1

Participants

5

Reactant 2

HCID 2724541Prolinol, (R)-HCID 68882624N-[5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine

Product 1

HCID 68880437HCID 68880437, compoundYield 182.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 80192-MethoxyethanolSolvent

Conditions

Temperature
110 °C

Procedure

N-[5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.165 g) was dissolved in 2-methoxyethanol (5 ml) then (R)-(−)-2-pyrrolidinemethanol (0.516 g) was added and the mixture heated to 110° C. for 50 minutes. The reaction mixture was cooled to room temperature and diluted with dichloromethane, washed with water and brine, dried over magnesium sulfate and then evaporated. The residue was purified by column chromatography on silica using increasingly polar mixtures of dichloromethane and methanol with methanolic ammonia as eluent. There was thus obtained the title compound (0.341 g) as a pale yellow gum; NMR Spectrum: (CDCl3) 1.761 (m, 3H), 1.88 (m, 1H), 2.12 (m, 2H), 2.30 (m, 1H), 2.48 (m, 1H), 2.63 (m, 1H), 3.04 (m, 1H), 3.21 (m, 1H), 3.39 (dd, 1H), 3.46 (s, 3H), 3.64 (dd, 1H), 3.98 (s, 3H), 4.25 (m, 2H), 4.35 (s, 2H), 6.07 (s, 2H), 7.01 (s, 1H), 7.06 (s, 1H), 7.12 (s, 1H), 7.28 (s, 1H), 8.62 (s, 1H). Mass Spectrum: M+H+ 555/557.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. customevaporated
  5. customThe residue was purified by column chromatography on silica using
  6. temperatureincreasingly polar mixtures of dichloromethane and methanol with methanolic ammonia as eluent

Sources & evidence

ORD record
ord-b8a03a1f9a1a4767907e25eca9a9adfa
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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