Dimethyl Sulfoxide → [(S)-1-(2-Amino-9-fluoro-5-methyl-1,3-dioxo-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinazolin-8-yl)pyrrolidin-3-yl]carbamic acid tert-butyl ester

HRID 729421Notes

Reaction equation

HRID 729421 reaction equation
N[C:2]1([CH3:19])[N:13]2[C:14]3[C:9]([C:10](=[O:16])[NH:11][C:12]2=[O:15])=[CH:8][C:7]([F:17])=[C:6](F)[C:5]=3[CH2:4][CH2:3]1.[C:20]([O:24][C:25](=[O:32])[NH:26][C@H:27]1[CH2:31][CH2:30][NH:29][CH2:28]1)([CH3:23])([CH3:22])[CH3:21].C([N:35](CC)CC)C.CS(C)=O>O>[C:20]([O:24][C:25](=[O:32])[NH:26][C@H:27]1[CH2:31][CH2:30][N:29]([C:6]2[C:5]3[CH2:4][CH2:3][CH:2]([CH3:19])[N:13]4[C:14]=3[C:9]([C:10](=[O:16])[N:11]([NH2:35])[C:12]4=[O:15])=[CH:8][C:7]=2[F:17])[CH2:28]1)([CH3:23])([CH3:21])[CH3:22]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 219792245-amino-8,9-difluoro-5-methyl-6,7-dihydro-5H-pyrido[3,2,1-ij]quinazoline-1,3-dione

Product 1

HCID 58681896[(S)-1-(2-Amino-9-fluoro-5-methyl-1,3-dioxo-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinazolin-8-yl)pyrrolidin-3-yl]carbamic acid tert-butyl esterYield 71.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of 0.12 g (0.45 mmol) of 5-amino-8,9-difluoro-5-methyl-6,7-dihydro-5H-pyrido[3,2,1-ij]quinazoline-1,3-dione (Example 24i), 0.34 g (1.8 mmol) of (S)-3-pyrrolidinylcarbamic acid tert-butyl ester (J. Med. Chem., 1992; 35:1764), 0.2 g (2.0 mmol) of triethylamine and 7 mL of dimethyl sulfoxide is heated at 110° C. for 18 hours. The reaction is cooled to room temperature, diluted with 80 mL of ice and water and stirred at 5° C. for 1 hour. The resulting precipitate is removed by filtration, washed with water and dried in vacuo. The solid is chromatographed over flash grade silica gel (230-400 mesh) eluting with dichloromethane/ethanol (9:1) to give 0.14 g of the title compound, mp 98-100° C.

Workup

  1. customThe resulting precipitate is removed by filtration
  2. washwashed with water
  3. customdried in vacuo
  4. customThe solid is chromatographed over flash grade silica gel (230-400 mesh)
  5. washeluting with dichloromethane/ethanol (9:1)

Sources & evidence

ORD record
ord-c3435451afa547ff9ea16137bec283f9
Source dataset
uspto-grants-2009_09
Patent number
US07582627B2

Reaction notes

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