Dichloromethane → HCID 71257931, compound

HRID 337290Notes

Reaction equation

HRID 337290 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]([S:38]([CH3:41])(=[O:40])=[O:39])=[CH:34][N:33]=4)[C:28](=[O:42])[N:27]([CH3:43])[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]([S:38]([CH3:41])(=[O:40])=[O:39])=[CH:34][N:33]=4)[C:28](=[O:42])[N:27]([CH3:43])[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 86676934HCID 86676934, compound

Product 1

HCID 71257931HCID 71257931, compoundYield 58.1%

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-(methylsulfonyl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde (154 mg, 256 μmol, Eq: 1.00) was combined with dichloromethane (24 ml) and 2 mL MeOH. Sodium borohydride (14.5 mg, 383 μmol, Eq: 1.5) was added and the reaction suspension was stirred at ambient temperature for 1 h. 1 mL of saturated NH4Cl was added; followed by 5 mL H2O. The mixture was stirred for 5 min. The reaction mixture was poured into 50 mL H2O and extracted with dichloromethane (3×50 mL). The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 12 g, 1% to 3% MeOH in DCM) to afford the desired product (90 mg) as a white powder. (M+H)+=605 m/e. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.46 (s, 9 H) 3.10 (s, 3 H) 3.77 (s, 3 H) 4.51 (br. s., 2 H) 6.94 (d, J=8.59 Hz, 1 H) 7.48-7.65 (m, 3 H) 7.88 (d, J=2.53 Hz, 1 H) 8.00 (dd, J=8.59, 2.53 Hz, 1 H) 8.33-8.45 (m, 2 H) 8.71 (d, J=5.05 Hz, 1 H) 8.82 (d, J=2.53 Hz, 1 H) 8.92 (d, J=2.53 Hz, 1 H).

Workup

  1. stirringThe mixture was stirred for 5 min
  2. extractionextracted with dichloromethane (3×50 mL)
  3. dry with materialThe organic layers were dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by flash chromatography (silica gel, 12 g, 1% to 3% MeOH in DCM)

Sources & evidence

ORD record
ord-8c6ad4d14f314655b276113e9da83041
Source dataset
uspto-grants-2014_11
Patent number
US08889682B2

Reaction notes

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