Dichloromethane → HCID 71257880, compound

HRID 337289Notes

Reaction equation

HRID 337289 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[N:24]=[CH:23][CH:22]=[C:21]([C:25]3[CH:30]=[C:29]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([C:38]([N:40]5[CH2:45][CH2:44][O:43][CH2:42][CH2:41]5)=[O:39])=[CH:34][N:33]=4)[C:28](=[O:46])[N:27]([CH3:47])[CH:26]=3)[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].ClCCl.[BH4-].[Na+].[NH4+].[Cl-]>O.CO>[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:18]([CH2:19][OH:20])=[C:21]([C:25]3[CH:30]=[C:29]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([C:38]([N:40]5[CH2:45][CH2:44][O:43][CH2:42][CH2:41]5)=[O:39])=[CH:34][N:33]=4)[C:28](=[O:46])[N:27]([CH3:47])[CH:26]=3)[CH:22]=[CH:23][N:24]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 86676933HCID 86676933, compound

Product 1

HCID 71257880HCID 71257880, compoundYield 81.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

In a 250 mL round-bottomed flask, 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-(morpholine-4-carbonyl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde (50 mg, 78.4 μmol, Eq: 1.00) was combined with dichloromethane (6 ml) and 2 mL MeOH to give a yellow solution. Sodium borohydride (3.56 mg, 94.1 μmol, Eq: 1.2) was added. The colorless solution was stirred at ambient temperature for 1 h. 1 mL of saturated NH4Cl was added; followed by 5 mL H2O. Mixture was stirred for 5 min. The reaction mixture was poured into 50 mL H2O and extracted with EtOAc (3×50 mL). The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 24 g, 1% to 3% MeOH in DCM) to afford the desired product (41 mg) as an off-white powder. (M+H)+=640 m/e. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.46 (s, 9 H) 3.50-3.85 (s and overlapping m, 11 H) 4.51 (br. s., 2 H) 6.90 (d, J=8.59 Hz, 1 H) 7.51-7.63 (m, 3 H) 7.71 (dd, J=8.59, 2.53 Hz, 1 H) 7.79 (d, J=2.53 Hz, 1 H) 8.26 (br. s., 1 H) 8.37 (d, J=1.52 Hz, 2 H) 8.70 (d, J=5.05 Hz, 1 H) 8.82 (d, J=2.02 Hz, 1 H).

Workup

  1. customto give a yellow solution
  2. stirringMixture was stirred for 5 min
  3. extractionextracted with EtOAc (3×50 mL)
  4. dry with materialThe organic layers were dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (silica gel, 24 g, 1% to 3% MeOH in DCM)

Sources & evidence

ORD record
ord-4e7eeec5ba644a97a32ea40520735294
Source dataset
uspto-grants-2014_11
Patent number
US08889682B2

Reaction notes

Loading…