Trimethyl orthoacetate → 3-methyl-9-phenyl-8-(4-((4-(5-(pyridin-2-yl)-1H-1,2,4-triazol-3-yl)piperidin-1-yl)methyl)phenyl)-[1,2,4]triazolo[3,4-f][1,6]naphthyridine

HRID 1678730Notes

Reaction equation

[NH:1]([C:3]1[N:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[C:6]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:7]([C:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:20]3[CH2:25][CH2:24][CH:23]([C:26]4[N:30]=[C:29]([C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=5)[NH:28][N:27]=4)[CH2:22][CH2:21]3)=[CH:15][CH:14]=1)=[N:8]2)[NH2:2].[C:43](OC)(OC)(OC)[CH3:44]>CN(C=O)C>[CH3:43][C:44]1[N:12]2[C:3]([C:4]3[CH:5]=[C:6]([C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=4)[C:7]([C:13]4[CH:18]=[CH:17][C:16]([CH2:19][N:20]5[CH2:21][CH2:22][CH:23]([C:26]6[N:30]=[C:29]([C:31]7[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=7)[NH:28][N:27]=6)[CH2:24][CH2:25]5)=[CH:15][CH:14]=4)=[N:8][C:9]=3[CH:10]=[CH:11]2)=[N:1][N:2]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To 5-hydrazino-3-phenyl-2-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)-1,6-naphthyridine (2-1) (55 mg, 0.101 mmol) in DMF (1.0 mL) was added trimethyl orthoacetate (0.63 mL, 5.04 mmol). The reaction mixture was stirred at 100° C. for 3 hours, and then concentrated in vacuo, and chromatographed to furnish the desired 3-methyl-9-phenyl-8-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]triazolo[3,4-f]-1,6-naphthyridine (2-2) (28 mg) as its trifluoroacetic acid salt. 1H NMR: (500 MHz, CDCl3) δ 8.87 (s, 1H), 8.65 (d, J=6.4 Hz, 1H), 8.33 (d, J=7.5 Hz, 1H), 8.11 (d, J=7.8 Hz, 1H), 7.92 (t, J=7.8 Hz, 1H), 7.49-7.41 (m, 3H), 7.36-7.30 (m, 8H), 3.61 (s, 2H), 3.02-3.00 (m, 2H), 3.00-2.84 (m, 1H), 2.25-2.21 (m, 2H), 2.10-1.83 (m, 4H), 1.97 (s, 3H).

Workup

concentrationconcentrated in vacuo
customchromatographed

Sources & evidence

ORD record: ord-d7bc316bb19947f2af208b4a299ad348
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08008317B2

Reaction notes

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