Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 5-[3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-1H-pyrrole-2-carboxylic acid amide

HRID 1025573Notes

Reaction equation

HRID 1025573 reaction equation
C[N:2](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:25]([C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][CH:38]=1)[C:35](=[O:39])[N:34]([C:40]1[C:41]([CH2:55][OH:56])=[C:42]([C:46]3[N:50]([CH3:51])[C:49]([C:52](O)=[O:53])=[CH:48][CH:47]=3)[CH:43]=[CH:44][CH:45]=1)[N:33]=[CH:32]2)([CH3:28])([CH3:27])[CH3:26]>C1COCC1>[C:25]([C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][CH:38]=1)[C:35](=[O:39])[N:34]([C:40]1[C:41]([CH2:55][OH:56])=[C:42]([C:46]3[N:50]([CH3:51])[C:49]([C:52]([NH2:2])=[O:53])=[CH:48][CH:47]=3)[CH:43]=[CH:44][CH:45]=1)[N:33]=[CH:32]2)([CH3:28])([CH3:26])[CH3:27]

Participants

4

Reactant 2

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 710086185-[3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-1H-pyrrole-2-carboxylic acid

Product 1

HCID 710081215-[3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-1H-pyrrole-2-carboxylic acid amideYield 22.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

HATU (110 mg, 0.288 mmol) was added to a solution of 5-[3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-1H-pyrrole-2-carboxylic acid (113 mg, 0.262 mmol) in dry THF (15 mL). Ammonia gas was bubbled through the solution. The mixture was stirred at room temperature under NH3 (g) for 16 h. The mixture was concentrated under reduced pressure. The residue was purified by preparative HPLC to give 5-[3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-1H-pyrrole-2-carboxylic acid amide (25 mg, yield 22%) as a white solid. 1H NMR (300 MHz, CD3OD) δ 8.42 (s, 1H), 8.27 (d, J=8.5 Hz, 1H), 8.02-7.90 (m, 2H), 7.54-7.35 (m, 2H), 7.24-7.13 (m, 2H), 7.02 (d, J=1.9 Hz, 1H), 4.37 (s, 2H), 3.87 (s, 3H), 1.37 (s, 9H). LC-MS calcd for C25H26N4O3 (m/e) 430.20, obsd 883 [2M+Na]+.

Workup

  1. customAmmonia gas was bubbled through the solution
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-52b2534bfaa94ce7b56ba531a4eae980
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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