Methanol → HCID 71257642, compound

HRID 337278Notes

Reaction equation

HRID 337278 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]([CH:38]5[CH2:43][CH2:42][N:41]([CH3:44])[CH2:40][CH2:39]5)=[CH:34][N:33]=4)[C:28](=[O:45])[N:27]([CH3:46])[N:26]=3)[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].C(Cl)Cl.CO.[BH4-].[Na+]>CCOCC.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:18]([CH2:19][OH:20])=[C:21]([C:25]3[CH:30]=[C:29]([NH:31][C:32]4[N:33]=[CH:34][C:35]([CH:38]5[CH2:39][CH2:40][N:41]([CH3:44])[CH2:42][CH2:43]5)=[CH:36][CH:37]=4)[C:28](=[O:45])[N:27]([CH3:46])[N: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 887MethanolHCID 6344DichloromethaneHCID 4311764Sodium borohydrideHCID 86676931HCID 86676931, compound

Product 1

HCID 71257642HCID 71257642, compoundYield 54.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a 250 mL round-bottomed flask, 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-(1-methylpiperidin-4-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)nicotinaldehyde (1.62 g, 2.6 mmol, Eq: 1.00) was combined with dry CH2Cl2 (45 ml) and dry MeOH (20 mL) to give a brown solution. Sodium borohydride (177 mg, 4.68 mmol, Eq: 1.8) was added and the reaction was stirred at ambient temperature for 1 h before being quenched with sat'd NH4Cl. The reaction mixture was diluted with 50 mL H2O and extracted with CH2Cl2 (3×150 mL). The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography [silica gel, 80 g, 0% to 50% (60:10:1 CH2Cl2:MeOH: NH40H) in CH2Cl2] to afford a slightly impure foam. The foam was slurried in ml Et2O and 10 ml EtOAc and stirred slowly with a heavy stir bar for 1 h resulting in a white solid. The solid was collected by filtration, dried under vacuum at 50° C. for 48 h. to afford the desired product as a white solid (880 mg). (M+H)+=625 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.44 (s, 9 H) 1.87 (br. s., 3 H) 2.15 (br. s., 2 H) 2.39 (br. s., 3 H) 2.52 (t, J=7.74 Hz, 1 H) 3.04 (br. s., 2 H) 3.82-3.91 (m, 1 H) 3.93 (s, 3 H) 4.46-4.63 (m, 2 H) 6.93 (d, J=8.69 Hz, 1 H) 7.42-7.59 (m, 3 H) 7.64 (d, J=4.91 Hz, 1 H) 8.15-8.39 (m, 3 H) 8.70 (s, 1 H) 8.73 (d, J=4.91 Hz, 1 H)

Workup

  1. customto give a brown solution
  2. custombefore being quenched with sat'd NH4Cl
  3. additionThe reaction mixture was diluted with 50 mL H2O
  4. extractionextracted with CH2Cl2 (3×150 mL)
  5. dry with materialThe organic layers were dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography [silica gel, 80 g, 0% to 50% (60:10:1 CH2Cl2:MeOH: NH40H) in CH2Cl2]
  8. customto afford a slightly impure foam
  9. customresulting in a white solid
  10. filtrationThe solid was collected by filtration
  11. customdried under vacuum at 50° C. for 48 h.

Sources & evidence

ORD record
ord-edd98c0a7ec948288c23822796f647bd
Source dataset
uspto-grants-2014_11
Patent number
US08889682B2

Reaction notes

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