Oxalyl chloride → HCID 76601334, compound

HRID 1174894Notes

Reaction equation

HRID 1174894 reaction equation
[C:1]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:6]=[CH:5][C:4]([C:7]([OH:9])=O)=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.[CH3:22][N:23]([CH3:39])[CH:24]1[CH2:28][CH2:27][N:26]([C:29]2[S:30][C:31]3[CH:37]=[C:36]([NH2:38])[CH:35]=[CH:34][C:32]=3[N:33]=2)[CH2:25]1>CN(C=O)C.C(Cl)Cl>[CH3:22][N:23]([CH3:39])[CH:24]1[CH2:28][CH2:27][N:26]([C:29]2[S:30][C:31]3[CH:37]=[C:36]([NH:38][C:7]([C:4]4[CH:3]=[CH:2][C:1]([C:10]5[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=5)=[CH:6][CH:5]=4)=[O:9])[CH:35]=[CH:34][C:32]=3[N:33]=2)[CH2:25]1

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 66724(1,1'-Biphenyl)-4-carboxylic acidHCID 632315072-(3-Dimethylamino-pyrrolidin-1-yl)-benzothiazol-6-ylamine

Product 1

HCID 76601334HCID 76601334, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent3×

Procedure

Combine 4-biphenylcarboxylic acid (0.124 g, 0.623 mmol), dichloromethane (5.0 mL), and DMF (3 drops) with stirring. Add oxalyl chloride (0.11 mL, 1.25 mmol) and stir the mixture for 2 h at room temperature. Concentrate the mixture in vacuo, add hexane (approximately 10 mL), re-concentrate in vacuo, and re-dissolve in CH2Cl2 (4.0 mL). Transfer the mixture to a 40 mL reaction vial and add a mixture of 2-(3-dimethylamino-pyrrolidin-1-yl)-benzothiazol-6-ylamine (0.109 g, 0.415 mmol) (Example 1, step 3) in CH2Cl2 (2.0 mL). Stir the mixture overnight at room temperature. Dilute the reaction mixture with CH2Cl2 (25 mL), wash with saturated NaHCO3 (aqueous) (25 mL), and extract the aqueous phase with CH2Cl2 (25 mL). Wash the combined organic phases with saturated NaHCO3 (aqueous) (2×25 mL), dry over sodium sulfate, filter, and concentrate in vacuo to yield a yellow solid. Purify the crude product using silica gel chromatography (40 g column, 5% MeOH/CH2Cl2) to afford the title compound (53 mg, 29%). mass spectrum (m/e): 443.4 [M+1], 441.3 [M−1]. 1H NMR (400 MHz, CDCl3): δ 8.69-8.58 (m, 1H), 8.26 (s, 1H), 7.93 (d, 2H, J=8.0 Hz), 7.67 (d, 2H, J=7.6 Hz), 7.59 (d, 2H, J=7.2 Hz), 7.50-7.26 (m, 5H), 3.81 (t, 1H, J=10.4 Hz), 3.72 (t, 1H, J=8.8 Hz), 3.52 (m, 1H), 3.43 (m, 1H), 3.01 (m, 1H), 2.35 (s, 6H), 2.29 (m, 1H), 2.04 (m, 1H).

Workup

  1. concentrationConcentrate the mixture in vacuo
  2. additionadd hexane (approximately 10 mL)
  3. concentrationre-concentrate in vacuo
  4. dissolutionre-dissolve in CH2Cl2 (4.0 mL)
  5. customTransfer the mixture to a 40 mL reaction vial
  6. additionadd
  7. washwash with saturated NaHCO3 (aqueous) (25 mL)
  8. extractionextract the aqueous phase with CH2Cl2 (25 mL)
  9. washWash the combined organic phases with saturated NaHCO3 (aqueous) (2×25 mL)
  10. dry with materialdry over sodium sulfate
  11. filtrationfilter
  12. concentrationconcentrate in vacuo
  13. customto yield a yellow solid
  14. customPurify the crude product

Sources & evidence

ORD record
ord-48a2fe8605f345b5a7be9a5dd18ba717
Source dataset
uspto-grants-2010_11
Patent number
US07838543B2

Reaction notes

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