Dimethylamine → 6-[4-(2-Tert-butoxycarbonylamino-2-dimethylcarbamoyl-ethyl)-phenoxy]-nicotinic acid methyl ester

HRID 273438Notes

Reaction equation

HRID 273438 reaction equation
[CH3:1][O:2][C:3](=[O:30])[C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([CH2:17][CH:18]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:19](O)=[O:20])=[CH:13][CH:12]=2)=[N:6][CH:5]=1.[CH2:31]([N:33](CC)[CH2:34]C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CNC>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:30])[C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([CH2:17][CH:18]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:27])[CH3:28])=[O:24])[C:19](=[O:20])[N:33]([CH3:34])[CH3:31])=[CH:13][CH:12]=2)=[N:6][CH:5]=1

Participants

6

Reactant 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 692036526-[4-(2-Tert-butoxycarbonylamino-2-carboxy-ethyl)-phenoxy]-nicotinic acid methyl ester

Product 1

HCID 692034916-[4-(2-Tert-butoxycarbonylamino-2-dimethylcarbamoyl-ethyl)-phenoxy]-nicotinic acid methyl esterYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The compound 17 (2.2 g, 5.28 mmol) was dissolved in CH2Cl2 and stirred at room temperature under an atmosphere of argon. Triethylamine (0.883 mL, 6.33 mmol) and benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP reagent, 2.5 g, 5.80 mmol) were added and the reaction mixture was stirred for 15 min. Dimethylamine (2.0 M solution in THF, 13.2 mL, 26.4 mmol) was added and the resulting solution was stirred at room temperature for about 2-3 h. The solvent was removed under reduced pressure and the resulting oil was taken up in EtOAc (200 mL). The organic layer was extracted with 0.5 N NaOH (1×30 mL), water (2×100 mL) and brine (1×100 mL). Drying and concentration of the organic layer gave the desired amide 18 (1.3 g, ˜98%). 1H NMR (400 MHz, DMSO-d6): 8.67 (br, 1H), 8.29 (dd, J=8.8 and 2.4 Hz, 1H) 7.31 (d, J=8.4 Hz, 2H), 7.11 (d, J=8.8 Hz, 1H), 7.08 (m, 3H), 4.57 (m, 1H), 3.85 (s, 3H), 2.93 (s, 3H), 2.85-2.75 (m, 2H), 2.80 (s, 3H), 1.32 (s, 9H).

Workup

  1. stirringthe reaction mixture was stirred for 15 min
  2. stirringthe resulting solution was stirred at room temperature for about 2-3 h
  3. customThe solvent was removed under reduced pressure
  4. extractionThe organic layer was extracted with 0.5 N NaOH (1×30 mL), water (2×100 mL) and brine (1×100 mL)
  5. customDrying

Sources & evidence

ORD record
ord-5412cf73d1d149a591c44e01ae3f5b27
Source dataset
uspto-grants-2008_11
Patent number
US07456292B2

Reaction notes

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