Triethylamine → 4-[3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1H-pyrrole-2-carboxylic acid amide

HRID 1025569Notes

Reaction equation

HRID 1025569 reaction equation
C[N:2](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[C:32]([C:36]1[CH:37]=[C:38]2[C:43](=[CH:44][CH:45]=1)[C:42](=[O:46])[N:41]([C:47]1[C:48]([CH2:61][OH:62])=[C:49]([C:53]3[CH:54]=[C:55]([C:58]([OH:60])=O)[NH:56][CH:57]=3)[CH:50]=[CH:51][CH:52]=1)[N:40]=[CH:39]2)([CH3:35])([CH3:34])[CH3:33]>C1COCC1>[C:32]([C:36]1[CH:37]=[C:38]2[C:43](=[CH:44][CH:45]=1)[C:42](=[O:46])[N:41]([C:47]1[C:48]([CH2:61][OH:62])=[C:49]([C:53]3[CH:54]=[C:55]([C:58]([NH2:2])=[O:60])[NH:56][CH:57]=3)[CH:50]=[CH:51][CH:52]=1)[N:40]=[CH:39]2)([CH3:33])([CH3:35])[CH3:34]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 710084124-[3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1H-pyrrole-2-carboxylic acid

Product 1

HCID 710083824-[3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1H-pyrrole-2-carboxylic acid amideYield 26.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

HATU (104 mg, 0.27 mmol) and triethyl amine (1 mL) were added to a solution of 4-[3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1H-pyrrole-2-carboxylic acid (95 mg, 0.23 mmol) in dry THF (15 mL). Ammonia gas was bubbled through the solution for 5 h. The mixture was concentrated under reduced pressure. The residue was purified by preparative TLC (petroleum ether/ethyl acetate=2:1) to give 4-[3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1H-pyrrole-2-carboxylic acid amide (25 mg, yield 26%) as a white solid. 1H NMR (300 MHz, CD3OD) δ 8.43 (s, 1H), 8.28 (d, J=8.5 Hz, 1H), 7.98-7.92 (m, 2H), 7.52-7.39 (m, 2H), 7.26-7.19 (m, 2H), 7.03 (d, J=1.6 Hz, 1H), 4.38 (s, 2H), 1.38 (s, 9H). LC-MS calcd for C24H24N4O3 (m/e) 416.18, obsd 417 [M+1]+.

Workup

  1. customAmmonia gas was bubbled through the solution for 5 h
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customThe residue was purified by preparative TLC (petroleum ether/ethyl acetate=2:1)

Sources & evidence

ORD record
ord-ff5d3a40f64d459d896d24290e340b6c
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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