Nitrogen → 3-(9-fluoro-2,3,3a,4-tetrahydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazin-7-yl)-2,6-dimethylpyrimidin-4(3H)-one

HRID 56108Notes

Reaction equation

HRID 56108 reaction equation
[F:1][C:2]1[C:11]2[N:10]3[CH2:12][CH2:13][CH2:14][CH:9]3[CH2:8][O:7][C:6]=2[CH:5]=[C:4]([NH2:15])[CH:3]=1.C[Al](C)C.N#N.[NH:22](/[C:26](/[CH3:32])=[CH:27]\[C:28](OC)=[O:29])[C:23]([CH3:25])=O>C(Cl)Cl>[F:1][C:2]1[C:11]2[N:10]3[CH2:12][CH2:13][CH2:14][CH:9]3[CH2:8][O:7][C:6]=2[CH:5]=[C:4]([N:15]2[C:28](=[O:29])[CH:27]=[C:26]([CH3:32])[N:22]=[C:23]2[CH3:25])[CH:3]=1

Participants

6

Reactant 4

HCID 947NitrogenHCID 57053602-Butenoic acid, 3-(acetylamino)-, methyl ester, (2Z)-HCID 16682925TrimethylaluminumHCID 731104369-fluoro-2,3,3a,4-tetrahydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazin-7-amine

Product 1

HCID 729483943-(9-fluoro-2,3,3a,4-tetrahydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazin-7-yl)-2,6-dimethylpyrimidin-4(3H)-oneYield 33%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 9-fluoro-2,3,3a,4-tetrahydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazin-7-amine (2.00 g, 9.61 mmol) in anhydrous CH2Cl2 (50 mL) was added trimethylaluminum (48 mL, 48 mmol, 1 M in heptane) slowly under N2. Upon the end of addition the mixture was stirred at rt for 40 min, followed by addition of a solution of methyl 3-acetaminocrotonate (2.66 g, 16.92 mmol) in anhydrous CH2Cl2 (30 mL) dropwise. The reaction mixture was stirred at rt for another 5 h, then quenched with an appropriate amount of water. The organic phase was washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo to give the title compound as a white solid (1.00 g, 33.0%). The compound was characterized by the following spectroscopic data:

Workup

  1. additionUpon the end of addition the mixture
  2. stirringThe reaction mixture was stirred at rt for another 5 h
  3. customquenched with an appropriate amount of water
  4. washThe organic phase was washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b72072a9cb5e4685a4d2a23a95e1ea74
Source dataset
uspto-grants-2016_09
Patent number
US09434695B2

Reaction notes

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