3-Fluorophenol → HCID 11442642, compound

HRID 1172559Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4](O)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].[NH2:11][C:12]1[N:17]2[N:18]=[C:19]([C:21]3[O:22][CH:23]=[CH:24][CH:25]=3)[N:20]=[C:16]2[N:15]=[C:14]([N:26]2[CH2:31][CH2:30][N:29]3[CH2:32][CH:33]([CH2:36][O:37]S(C)(=O)=O)[CH2:34][CH2:35][CH:28]3[CH2:27]2)[N:13]=1>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:7]=1[O:37][CH2:36][CH:33]1[CH2:32][N:29]2[CH2:30][CH2:31][N:26]([C:14]3[N:13]=[C:12]([NH2:11])[N:17]4[N:18]=[C:19]([C:21]5[O:22][CH:23]=[CH:24][CH:25]=5)[N:20]=[C:16]4[N:15]=3)[CH2:27][CH:28]2[CH2:35][CH2:34]1

Participants

Conditions

Temperature: 100 °C

Procedure

A solution containing 3-fluorophenol (1.5 eq.) in DMF was treated with sodium hydride (60% oil dispersion, 4 eq.) for 2 hours at around 50° C. A solution containing containing methanesulfonic acid 2-(7-amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)-octahydro-pyrido[1,2-a]pyrazin-7-ylmethyl ester (1 eq., see subpart (a) above) in DMF was added. The resulting mixture was then heated at around 100° C. for 24 hours. The solvent was removed, and the residue was dissolved in DMSO, filtered and purified by preparative HPLC using aqueous CH3CN (buffered with 0.1% TFA) to afford the desired product as a white powder: 1H NMR (400 Hz, DMSO-d6) δ 7.96 (d, J=2.0 Hz, 1H), 7.39 (m, 1H), 7.15 (d, J=3.0 Hz, 1H), 6.92-6.83 (m, 3H), 6.75 (dd, J=3.0, 2.0 Hz, 1H), 4.84 (m, 2H), 4.08 (dd, J=10.0, 5.0 Hz, 1H), 3.74 (dd, J=10.0, 7.0 Hz, 1H), 3.65 (m, 2H), 3.33 (m, 3H), 3.10 (m, 1H), 2.97 (m, 1H), 2.39 (m, 1H), 1.99 (m, 2H), 1.67 (m, 1H), 1.48 (m, 1H). MS m/z: 465 [M+H]+.

Workup

additionA solution containing
additionwas added
customThe solvent was removed
dissolutionthe residue was dissolved in DMSO
filtrationfiltered
custompurified by preparative HPLC

Sources & evidence

ORD record: ord-e8013604b2f644dc9ef248782f97aa64
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07834014B2

Reaction notes

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