N,N-Dimethyl-1,3-propanediamine → HCID 71538884, compound

HRID 1519305Notes

Reaction equation

HRID 1519305 reaction equation
C[O:2][C:3]([C:5]1[C:6]([C:24]2[CH:29]=[CH:28][C:27]([C:30](O)=[O:31])=[CH:26][CH:25]=2)=[CH:7][CH:8]=[C:9]([C:11]2[S:12][CH:13]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=3)[N:15]=2)[CH:10]=1)=[O:4].[CH3:33][N:34]([CH3:39])[CH2:35][CH2:36][CH2:37][NH2:38].C1COCC1.O.[OH-].[Li+]>CO.O>[Cl:23][C:18]1[CH:17]=[C:16]([C:14]2[N:15]=[C:11]([C:9]3[CH:10]=[C:5]([C:3]([OH:4])=[O:2])[C:6]([C:24]4[CH:29]=[CH:28][C:27]([C:30](=[O:31])[NH:38][CH2:37][CH2:36][CH2:35][N:34]([CH3:39])[CH3:33])=[CH:26][CH:25]=4)=[CH:7][CH:8]=3)[S:12][CH:13]=2)[CH:21]=[CH:20][C:19]=1[Cl:22]

Participants

7

Reactant 4

HCID 7993N,N-Dimethyl-1,3-propanediamineHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrate3×HCID 86679835HCID 86679835, compound2×

Product 1

HCID 71538884HCID 71538884, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Using the conditions of General Procedure D for Amide Coupling in Parallel Mode, 4-[4-(3,4-dichloro-phenyl)-thiazol-2-yl]-biphenyl-2,4′-dicarboxylic acid 2-methyl ester (which may be prepared as described for Intermediate 8; 100 mg, 0.21 mmol) was reacted with N,N-dimethyl-1,3-propanediamine (available from Aldrich Chemical Company, Inc.; 42 mg, 0.41 mmol) to give the crude amide product. The crude amide was hydrolyzed by adding THF (2 mL), water (0.05 mL), MeOH (1 mL), and lithium hydroxide monohydrate (12.3 mg, 0.29 mmol) and stirring the mixture overnight at room temperature. Lithium hydroxide monohydrate (22 mg, 0.52 mmol) was added. The reaction mixture was stirred overnight, and then another portion of lithium hydroxide monohydrate (22 mg, 0.52 mmol) was added. The reaction mixture was stirred overnight. The reaction mixture was concentrated to dryness under vacuum at 40° C. 1 M HCl (3 mL) was added, and the mixture was stirred, concentrated to dryness, and purified and purified using HPLC Purification Conditions A to give 4-[4-(3,4-dichloro-phenyl)-thiazol-2-yl]-4′-(3-dimethylamino-propylcarbamoyl)-biphenyl-2-carboxylic acid (102 mg, 89%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.16 (br s, 1H), 8.68 (t, J=5.6 Hz, 1H), 8.48 (s, 1H), 8.40 (d, J=1.8 Hz, 1H), 8.34 (d, J=2.0 Hz, 1H), 8.25 (dd, J=8.0, 1.8 Hz, 1H), 8.09 (dd, J=8.5, 2.0 Hz, 1H), 7.92 (d, J=8.3 Hz, 2H), 7.77 (d, J=8.3 Hz, 1H), 7.58 (d, J=8.0 Hz, 1H), 7.50 (d, J=8.3 Hz, 2H), 3.34-3.40 (m, 2H), 3.08-3.16 (m, 2H), 2.79-2.82 (m, 6H), 1.86-1.95 (m, 2H).

Workup

  1. customto give the crude amide product
  2. stirringThe reaction mixture was stirred overnight
  3. stirringThe reaction mixture was stirred overnight
  4. concentrationThe reaction mixture was concentrated to dryness under vacuum at 40° C
  5. addition1 M HCl (3 mL) was added
  6. stirringthe mixture was stirred
  7. concentrationconcentrated to dryness
  8. custompurified
  9. custompurified
  10. customHPLC Purification Conditions

Sources & evidence

ORD record
ord-b33b690c9dd14d2d965b4e080b91e981
Source dataset
uspto-grants-2015_07
Patent number
US09073881B2

Reaction notes

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