Ammonium Chloride → (R)-6-amino-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

HRID 519132Notes

Reaction equation

[CH3:1][C@H:2]1[N:15]2[C:6]([CH2:7][O:8][C:9]3[C:14]2=[CH:13][C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=3)=[N:5][NH:4][C:3]1=[O:19].[Cl-].[NH4+]>CO.C1COCC1.[Zn]>[NH2:16][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[O:8][CH2:7][C:6]1[N:15]2[C@H:2]([CH3:1])[C:3](=[O:19])[NH:4][N:5]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of (R)-4-methyl-6-nitro-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (50 g, 191 mmol) and ammonium chloride (102 g, 1907 mmol) in MeOH (700 mL) and THF (700 mL) was added zinc powder (125 g, 1907 mmol) in portions. After addition, the reaction mixture was stirred at 50° C. for 16 h. The reaction mixture was cooled to ambient temperature and filtered. The filter cake was washed with hot MeOH (3×1 L) and the combined organic phase was concentrated in vacuo. The residue was washed with THF (3×500 mL) and the combined organic phase was concentrated to give the crude (R)-6-amino-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (50 g, 215 mmol, containing residual NH4Cl), which was used in the next step without further purification. 1H NMR (CDCl3, 400 MHz): δ 6.68 (d, J=8.4 Hz, 1H), 6.43 (d, J=2.4 Hz, 1H), 6.16 (dd, J=2.4, 8.4 Hz, 1H), 4.83 (br. s., 1H), 4.56-4.52 (m, 1H), 4.47-4.39 (m, 2H), 1.31 (d, J=6.5 Hz, 3H). LCMS (Table 1, Method 3) Rt=0.803 min; MS m/z: 233 [M+H]+.

Workup

additionAfter addition
temperatureThe reaction mixture was cooled to ambient temperature
filtrationfiltered
washThe filter cake was washed with hot MeOH (3×1 L)
concentrationthe combined organic phase was concentrated in vacuo
washThe residue was washed with THF (3×500 mL)
concentrationthe combined organic phase was concentrated

Sources & evidence

ORD record: ord-885cb83eb7bb4336845eb9b10944212a
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115151B2

Reaction notes

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