Methane → 300843-20-3

HRID 2119315Notes

Reaction equation

HRID 2119315 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([CH2:17][C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)=[N:9][N:8]=2)=[CH:4][CH:3]=1.C.C[OH:28]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([C:17]([C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)=[O:28])=[N:9][N:8]=2)=[CH:24][CH:25]=1

Participants

4

Reactant 3

HCID 297MethaneHCID 887MethanolHCID 151194Vatalanib2×

Product 1

HCID 22386458300843-20-3

Procedure

Heating of a mixture of 1-(4-chloranilino)-4-(4-pyridylmethyl)-phthalazine (Example 4 in WO 98/35958) and charcoal in boiling methanol for about 7 days in an open vessel leads to partial oxidation of the methylen-bridge of 1-(4-chloranilino)-4-(4-pyridylmethyl)-phthalazine. After cooling to RT, unchanged 1-(4-chloranilino)-4-(4-pyridylmethyl)-phthalazine crystallizes out and can be filtered off. Chromatography (SiO2; dichloromethane/methanol 98:2) of the concentrated filtrate then leads to [4-(4-chloranilino)phthalazin-1-yl](pyridin-4-yl)ketone and rac. [4-(4-chloranilino)phthalazin-1-yl](pyridin-4-yl)methanol (see Expl. 78 in WO 98/35958). [4-(4-Chloranilino)phthalazin-1-yl](pyridin-4-yl)ketone: 1H NMR (DMSO-d6) δ9.88 (bs, 1H, HN), 8.79 (d, 2H, pyridine), 8.71 (d, 1H), 8.63 (d, 1H), 8.07 (m, 2H), 7.97 (d, 2H, chloranilino), 7.77 (d, 2H, pyridine), 7.45 (d, 2H, chloranilino); IR (KBr): 3287, 3139, 3066, 1667 (CO), 1620 cm−1; FAB MS (M+H)+=361. rac [4-(4-Chloranilino)phthalazin-1-yl](pyridin-4-yl)methanol: m.p. 197-197.5 dec; 1H NMR (DMSO-d6) δ9.32 (bs, 1H, HN), 8.57 (d, 1H), 8.49 (d, 2H, pyridine), 8.22 (d, 1 H), 8.00 (d, 2H, chloranilino), 7.93 (m, 1H), 7.84 (m, 1H), 7.41 (d, 2H, pyridine); 7.40 (d, 2H, chloranilino), 6.77 (d, 1H, HO), 6.30 (d, 1H, HC-OH); IR (KBr): 3386 (OH), 3122, 2852, 1619, 1600, 1521, 1493, 1406 cm−1; FAB MS (M+H)+=363.

Workup

  1. customfor about 7 days
  2. customunchanged 1-(4-chloranilino)-4-(4-pyridylmethyl)-phthalazine crystallizes out
  3. filtrationcan be filtered off

Sources & evidence

ORD record
ord-5334dbd97c8a4f16b46aee2959a7d3a9
Source dataset
uspto-grants-2004_02
Patent number
US06686347B2

Reaction notes

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