Formaldehyde → HCID 178425789, compound

HRID 1488064Notes

Reaction equation

HRID 1488064 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]2[NH:6][C:7]([C:11]3[CH:12]=[C:13]([CH:28]=[CH:29][C:30]=3[CH3:31])[C:14]([N:16]3[CH2:19][CH:18]([C:20]4[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=4)[CH2:17]3)=[O:15])=[C:8]([CH3:10])[N:9]=2)[CH2:2]1.C=O.[BH3-][C:35]#N.[Na+]>O1CCCC1>[CH3:31][C:30]1[CH:29]=[CH:28][C:13]([C:14]([N:16]2[CH2:17][CH:18]([C:20]3[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=3)[CH2:19]2)=[O:15])=[CH:12][C:11]=1[C:7]1[NH:6][C:5]([CH:3]2[CH2:4][N:1]([CH3:35])[CH2:2]2)=[N:9][C:8]=1[CH3:10]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 178425788HCID 178425788, compound2×

Product 1

HCID 178425789HCID 178425789, compoundYield 3.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Into a 50-mL round-bottom flask, was placed a solution of 4-(1-(3-(2-(azetidin-3-yl)-4-methyl-1H-imidazol-5-yl)-4-methylbenzoyl)azetidin-3-yl)benzonitrile (compound 189.2, 50 mg, 0.12 mmol) in tetrahydrofuran (1 mL). Formaldehyde (65 μL, 37% wt, 0.57 mmol) and NaBH3CN (30 mg, 0.48 mmol) were added to the reaction. The reaction mixture was stirred for 1 h at room temperature. The reaction mixture was extracted with 3×3 mL of ethyl acetate and the combined organic extracts were washed with 3×1 mL of brine and concentrated under reduced pressure. The crude product (20 mg) was purified by Prep-HPLC with the following conditions (Prep-HPLC-020): Column, XBridge Prep C18 OBD Column, 5 μm, 19*150 mm; mobile phase, WATER WITH 0.03% NH3H2O and MeCN (26.0% MeCN up to 40.0% in 7 min, up to 100.0% in 2 min, down to 26.0% in 1 min); Detector, Waters 2489, 254 and 220 nm. This resulted in 1.8 mg (3%) of the title compound as a white solid. m/z (ES+) 426 (M+H)+.

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. extractionThe reaction mixture was extracted with 3×3 mL of ethyl acetate
  3. washthe combined organic extracts were washed with 3×1 mL of brine
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product (20 mg) was purified by Prep-HPLC with the following conditions (Prep-HPLC-020)
  6. waitmobile phase, WATER WITH 0.03% NH3H2O and MeCN (26.0% MeCN up to 40.0% in 7 min
  7. waitup to 100.0% in 2 min
  8. waitdown to 26.0% in 1 min)

Sources & evidence

ORD record
ord-235b7742e287494d993529bef868d488
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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