HCID 45257321, compound → HCID 178433352, compound

HRID 1917483Notes

Reaction equation

[NH2:1][C:2]1[N:3]=[C:4]([CH3:21])[C:5]2[C:11](=S)[NH:10][C@@H:9]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=3[Br:20])[CH2:8][C:6]=2[N:7]=1.[O:22]1[CH2:27][CH2:26][O:25][CH2:24][C@@H:23]1[CH2:28][O:29][NH2:30]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Hg+2].C([O-])(=O)C>[O:22]1[CH2:27][CH2:26][O:25][CH2:24][C@@H:23]1[CH2:28][O:29]/[N:30]=[C:11]1\[NH:10][C@@H:9]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=2[Br:20])[CH2:8][C:6]2[N:7]=[C:2]([NH2:1])[N:3]=[C:4]([CH3:21])[C:5]\1=2

Participants

Conditions

Temperature: 100 °C

Procedure

Thiolactam (31I (Example 31), 0.087 g, 0.0272 mmol), (R)—O-((1,4-dioxan-2-yl)methyl)hydroxylamine (2M (Example 2-E), 0.145 g, 1.09 mmol), and mercury (II) acetate (0.173 g, 0.045 mmol) were dissolved in 3.5 mL of dry toluene and heated in 100° C. oil bath for 1 h. The reaction was done as judged by LC/MS. The crude mixture was filtered through Celite, rinsed with methanol and then concentrated and purified on preparatory LC/MS (25-55% CH3CN in H2O) to afford (R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O—((R)-1,4-dioxan-2-yl)methyl oxime (39A, 0.0405 g, 36.7% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.90 (s, 3H) 3.04 (dd, J=17.05, 8.97 Hz, 2H) 3.28 (dd, J=17.56, 4.17 Hz, 1H) 3.43 (dd, J=11.62, 9.85 Hz, 1H) 3.58-3.68 (m, 1H) 3.70-3.76 (m, 2H) 3.77-3.88 (m, 2H) 3.93-4.00 (m, 1H) 4.01-4.08 (m, 1H) 4.09-4.18 (m, 1H) 5.01 (d, J=5.05 Hz, 1H) 5.78 (s, 1H) 7.11 (td, J=8.21, 2.53 Hz, 1H) 7.37 (dd, J=7.96, 2.65 Hz, 1H) 7.41 (dd, J=8.84, 5.81 Hz, 1H). ESI-MS: m/z 468.1 (M+H)+.

Workup

filtrationThe crude mixture was filtered through Celite
washrinsed with methanol
concentrationconcentrated
custompurified on preparatory LC/MS (25-55% CH3CN in H2O)

Sources & evidence

ORD record: ord-0b2e0f5b6bc54d5a97bcbef4594c365e
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08618290B2

Reaction notes

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