Benzene → N-(4-(7-methoxy-1,5-naphthyridin-4-ylthio)phenyl)-4-(2-(piperidin-2-yl)ethoxy)phthalazin-1-amine

HRID 1042912Notes

Reaction equation

HRID 1042912 reaction equation
[H-].[Na+].[NH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[CH2:9][CH2:10][OH:11].C1C=CC=CC=1.Cl[C:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([S:36][C:37]3[C:46]4[C:41](=[CH:42][C:43]([O:47][CH3:48])=[CH:44][N:45]=4)[N:40]=[CH:39][CH:38]=3)=[CH:32][CH:31]=2)=[N:21][N:20]=1>>[CH3:48][O:47][C:43]1[CH:42]=[C:41]2[C:46]([C:37]([S:36][C:33]3[CH:34]=[CH:35][C:30]([NH:29][C:22]4[C:23]5[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=5)[C:19]([O:11][CH2:10][CH2:9][CH:4]5[CH2:5][CH2:6][CH2:7][CH2:8][NH:3]5)=[N:20][N:21]=4)=[CH:31][CH:32]=3)=[CH:38][CH:39]=[N:40]2)=[N:45][CH:44]=1

Participants

5

Reactant 4

HCID 241BenzeneHCID 151442-Piperidin-2-ylethanolHCID 24758Sodium hydrideHCID 866286644-chloro-N-(4-(7-methoxy-1,5-naphthyridin-4-ylthio)phenyl)phthalazin-1-amine

Product 1

HCID 59427329N-(4-(7-methoxy-1,5-naphthyridin-4-ylthio)phenyl)-4-(2-(piperidin-2-yl)ethoxy)phthalazin-1-amine

Conditions

Temperature
40 °C

Procedure

Sodium Hydride (11 mg, 449 μmol), 2-(piperidin-2-yl)ethanol (58 mg, 449 μmol), and benzene (2243 μl, 449 μmol) were combined in a resealable tube capped with a septum and heated to 40° C. for 30 minutes. 4-Chloro-N-(4-(7-methoxy-1,5-naphthyridin-4-ylthio)phenyl)phthalazin-1-amine (200 mg, 449 μmol) was added, and the reaction mixture was allowed to stir at 80° C. for 18 hours. The mixture was concentrated in vacuo and the crude material was partitioned between methylene chloride and water. The organic layers were combined and over Na2SO4 and concentrated. The crude material was purified via ISCO, 12 g RediSep column eluting with a 20-100% gradient of 90:10:1 (DCM:MeOH:NH4OH) in DCM. The product fractions were combined and concentrated in vacuo to afford N-(4-(7-methoxy-1,5-naphthyridin-4-ylthio)phenyl)-4-(2-(piperidin-2-yl)ethoxy)phthalazin-1-amine MS: [M+H]=539.

Workup

  1. customcapped with a septum
  2. concentrationThe mixture was concentrated in vacuo
  3. customthe crude material was partitioned between methylene chloride and water
  4. concentrationconcentrated
  5. customThe crude material was purified via ISCO, 12 g RediSep column
  6. washeluting with a 20-100% gradient of 90:10:1 (DCM:MeOH:NH4OH) in DCM
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b9155910af9f49249f9e73060661a87e
Source dataset
uspto-grants-2013_10
Patent number
US08557816B2

Reaction notes

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