Methanol → 4-[2-(6-tert-Butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-3-hydroxymethyl-pyridin-4-yl]-1-methyl-1H-pyrrole-2-carboxylic acid amide

HRID 1025599Notes

Reaction equation

HRID 1025599 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[C:22]([CH:23]=[O:24])=[C:21]([C:25]3[CH:26]=[C:27]([C:31]([NH2:33])=[O:32])[N:28]([CH3:30])[CH:29]=3)[CH:20]=[CH:19][N:18]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].C(Cl)Cl.CO.[BH4-].[Na+]>CCOC(C)=O>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[C:22]([CH2:23][OH:24])=[C:21]([C:25]3[CH:26]=[C:27]([C:31]([NH2:33])=[O:32])[N:28]([CH3:30])[CH:29]=3)[CH:20]=[CH:19][N:18]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 887MethanolHCID 6344DichloromethaneHCID 4311764Sodium borohydrideHCID 866737144-(2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-3-formylpyridin-4-yl)-1-methyl-1H-pyrrole-2-carboxamide

Product 1

HCID 710081594-[2-(6-tert-Butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-3-hydroxymethyl-pyridin-4-yl]-1-methyl-1H-pyrrole-2-carboxylic acid amideYield 50%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

In a 25 mL pear-shaped flask, 4-(2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-3-formylpyridin-4-yl)-1-methyl-1H-pyrrole-2-carboxamide (28 mg, 62.6 μmol, Eq: 1.00) was combined with CH2Cl2 (3 ml) and MeOH (1 ml) to give a colorless solution. Sodium borohydride (4.73 mg, 125 μmol, Eq: 2.00) was added. The reaction mixture was stirred for 1 h. The reaction mixture was poured into EtOAc (25 mL) and extracted with sat NH4Cl (3×10 mL). The organic layers were dried over MgSO4 and concentrated in vacuo followed by lyophilization to give 4-[2-(6-tert-Butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-3-hydroxymethyl-pyridin-4-yl]-1-methyl-1H-pyrrole-2-carboxylic acid amide (14 mg, 50%) as a white solid. 1H NMR (DMSO-d6) δ ppm 8.52 (d, J=2.8 Hz, 1H), 8.46 (d, J=5.0 Hz, 1H), 7.90 (d, J=1.8 Hz, 1H), 7.77 (dd, J=13.3, 1.8 Hz, 1H), 7.55-7.72 (m, 1H), 7.52 (d, J=5.0 Hz, 1H), 7.49 (d, J=1.8 Hz, 1H), 7.23 (d, J=2.0 Hz, 1H), 7.04 (br. s., 1H), 4.88 (br. s., 1H), 4.29-4.57 (m, 2H), 3.91 (s, 3H), 1.39 (s, 9H); MS m/e 450.5 (M+H+).

Workup

  1. customto give a colorless solution
  2. extractionextracted with sat NH4Cl (3×10 mL)
  3. dry with materialThe organic layers were dried over MgSO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6692a0d01ace4805a928aae123ab0a47
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

Loading…