3-(Dimethylamino)benzaldehyde → HCID 178482749, compound

HRID 591971

Reaction equation

HRID 591971 reaction equation
[NH2:1][C:2]1[C:7]([NH2:8])=[C:6]([NH:9][C@@H:10]2[C@@H:15]3[CH2:16][C@@H:12]([CH:13]=[CH:14]3)[C@@H:11]2[C:17]([NH2:19])=[O:18])[CH:5]=[CH:4][N:3]=1.[CH3:20][N:21]([CH3:30])[C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[CH:25]=O.C([O-])(=O)C.[NH4+]>C(O)C>[CH3:20][N:21]([CH3:30])[C:22]1[CH:23]=[C:24]([C:25]2[NH:1][C:2]3=[N:3][CH:4]=[CH:5][C:6]([NH:9][C@@H:10]4[C@@H:15]5[CH2:16][C@@H:12]([CH:13]=[CH:14]5)[C@@H:11]4[C:17]([NH2:19])=[O:18])=[C:7]3[N:8]=2)[CH:27]=[CH:28][CH:29]=1

Participants

5

Reactant 3

HCID 342883-(Dimethylamino)benzaldehydeHCID 517165Ammonium AcetateHCID 117701640HCID 117701640, compound

Product 1

HCID 178482749HCID 178482749, compoundYield 37.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(1S,2S,3R,4R)-3-(2,3-Diamino-pyridin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide (50.0 mg, 0.193 mmol) and 3-dimethylamino-benzaldehyde (31.6 mg, 0.212 mmol) were combined with ammonium acetate (29.7 mg, 0.386 mmol) and heated in ethanol (2.5 mL) at 70° C. for 18 h. The reaction mixture was concentrated and chromatographed by reverse phase preparative HPLC. The desired fractions were neutralized with bicarb solution and extracted into EtOAc. The organic layer was dried over MgSO4, filtered and concentrated. This residue was triturated in ethyl ether and filtered to yield 28 mg (37%) of the title compound. mp: 200-204° C., 1H NMR (300 MHz, DMSO-d6): 13.02 (s, 1H), 7.90 (d, 1H), 7.66 (s, 1H), 7.50 (s, 1H), 7.47 (d, J=8 Hz, 1H), 7.30 (t, J=8 Hz, 1H), 7.15 (s, 1H), 6.86 (m, 1H), 6.81 (d, J=8 Hz, 1H), 6.40 (d, J=5 Hz, 1H), 6.33 (s, 2H), 2.98 (s, 6H), 2.87 (s, 1H), 2.77 (s, 1H), 2.60 (d, J=8 Hz, 1H), 2.24 (d, J=8 Hz, 1H), 1.42 (d, J=8 Hz, 1H). HPLC: 1.63 min (G method), MS: 389 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customchromatographed by reverse phase preparative HPLC
  3. extractionextracted into EtOAc
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThis residue was triturated in ethyl ether
  8. filtrationfiltered

Sources & evidence

ORD record
ord-e0796d679f8e49f4bcdfa21ce0e51f25
Source dataset
uspto-grants-2016_01
Patent number
US09238656B2

Linked notes

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