Triethylamine → (S)-methyl 4-(1-(5-chloro-2-(3-(4-fluorophenoxy)azetidin-1-yl)nicotinamido)ethyl)benzoate

HRID 72490Notes

Reaction equation

HRID 72490 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:11]2[CH2:14][CH:13]([O:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[CH2:12]2)=[C:6]([CH:10]=1)[C:7](O)=[O:8].Cl.C(N=C=NCCCN(C)C)C.Cl.[NH2:36][C@H:37]([C:39]1[CH:48]=[CH:47][C:42]([C:43]([O:45][CH3:46])=[O:44])=[CH:41][CH:40]=1)[CH3:38].C(N(CC)CC)C.C([O-])(O)=O.[Na+]>ClCCl>[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:11]2[CH2:12][CH:13]([O:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[CH2:14]2)=[C:6]([CH:10]=1)[C:7]([NH:36][C@H:37]([C:39]1[CH:48]=[CH:47][C:42]([C:43]([O:45][CH3:46])=[O:44])=[CH:41][CH:40]=1)[CH3:38])=[O:8]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57462942(S)-Methyl 4-(1-aminoethyl)benzoate hydrochlorideHCID 679580475-Chloro-2-(3-(4-fluorophenoxy)azetidin-1-yl)nicotinic acid

Product 1

HCID 67958252(S)-methyl 4-(1-(5-chloro-2-(3-(4-fluorophenoxy)azetidin-1-yl)nicotinamido)ethyl)benzoateYield 89.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 5-chloro-2-(3-(4-fluorophenoxy)azetidin-1-yl)nicotinic acid (D102) (75 mg, 0.232 mmol) 1-Hydroxybenzotriazole hydrate (31.34 mg, 0.232 mmol) and 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (66.8 mg, 0.35 mmol) in dichloromethane (3 ml) was stirred 1 h at room temperature. A solution (S)-methyl 4-(1-aminoethyl)benzoate (D3) (50 mg, 0.232 mmol) and triethylamine (0.03 ml, 0.232 mmol) in dichloromethane (1 ml) was added and the resulting mixture was stirred overnight at room temperature. NaHCO3 sat. sol. (5 ml) was added and the mixture was extracted with dichloromethane (3×10 ml). Collected organics, after solvent evaporation were purified by SPE-Si (10 g) eluting with a mixture Cyclohexane/ethylacetate from 95/05 to 60/40. Collected fractions, after solvent evaporation, afforded the title compound (D146) (100 mg).

Workup

  1. stirringthe resulting mixture was stirred overnight at room temperature
  2. extractionthe mixture was extracted with dichloromethane (3×10 ml)
  3. customCollected organics, after solvent evaporation
  4. customwere purified by SPE-Si (10 g)
  5. washeluting with a mixture Cyclohexane/ethylacetate from 95/05 to 60/40
  6. customCollected fractions, after solvent evaporation

Sources & evidence

ORD record
ord-e8a45cd97aca4db684d6ea6e5ec381f9
Source dataset
uspto-grants-2014_09
Patent number
US08828987B2

Reaction notes

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