Benzenesulfonyl chloride → HCID 58869098, compound

HRID 1623145Notes

Reaction equation

HRID 1623145 reaction equation
[CH2:1]([C:4]1[N:5]([CH2:17][CH2:18][CH2:19][C:20](=O)[CH3:21])[C:6]2[C:15]3[N:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N:9]=[CH:8][C:7]=2[N:16]=1)[CH2:2][CH3:3].[CH2:23]([C:26]1[N:27](CCCC=O)C2C3C=CC=CC=3N=CC=2N=1)CC.[OH-:44].[Na+].[OH-:46].[NH4+:47].[C:48]1(C)C=CC(S(Cl)(=O)=O)=CC=1.C1(S(Cl)(=O)=O)C=CC=CC=1>>[NH2:47][C:8]1[C:7]2[N:16]=[C:4]([CH2:1][CH2:2][CH3:3])[N:5]([CH2:17][CH2:18][CH2:19][CH:20]([N:27]([O:46][CH3:48])[C:26](=[O:44])[CH3:23])[CH3:21])[C:6]=2[C:15]2[N:14]=[CH:13][CH:12]=[CH:11][C:10]=2[N:9]=1

Participants

7

Reactant 6

HCID 7369Benzenesulfonyl chlorideHCID 73974-Toluenesulfonyl chloride2×HCID 14798Sodium HydroxideHCID 14923Ammonium HydroxideHCID 57464096HCID 57464096, compoundHCID 69507057HCID 69507057, compound

Product 1

HCID 58869098HCID 58869098, compound

Conditions

Temperature
0 °C

Procedure

A modified version of the general methods described in Parts D-G of Example 6 was sequentially followed with 5-(2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)-pentan-2-one (5.27 g, 17.8 mmol) used in lieu of 4-(2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)butyraldehyde as the starting substrate. The formation of the O-methyl oxime, analogous to Part D of Example 6, was performed in the absence of sodium hydroxide and the pH of the reaction mixture was adjusted to ˜8 after completion of the reaction. The reduction of the oxime, analogous to Part E of Example 6, was complete after running overnight. Prior to addition of the ammonium hydroxide in the step analogous to Part G of Example 6, the reaction mixture was cooled to 0° C. and para-toluenesulfonyl chloride (1.1 eq) was substituted for phenylsulfonyl chloride. The reaction was incomplete after an hour, and additional para-toluenesulfonyl chloride (0.5 eq) was added. After the final step in the sequence, purification by HPFC (0-30% CMA in chloroform), trituration from acetonitrile, filtration, and drying of the material in a vacuum oven at 80° C. afforded 77 mg of N-[4-(4-amino-2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)1-methyl-butyl]-N-methoxyacetamide as an off-white powder, mp 158-159° C. Anal. calcd for C20H28N6O2: C, 62.48; H, 7.34; N, 21.86. Found: C, 62.19; H, 7.61; N, 22.09.

Workup

  1. customafter completion of the reaction
  2. waitThe reaction was incomplete after an hour
  3. customAfter the final step in the sequence, purification by HPFC (0-30% CMA in chloroform), trituration
  4. filtrationfrom acetonitrile, filtration
  5. customdrying of the material in a vacuum oven at 80° C.

Sources & evidence

ORD record
ord-e917dfe1d0ae4db6aa0be820896a1e87
Source dataset
uspto-grants-2014_07
Patent number
US08778963B2

Reaction notes

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