Pivalic acid → HCID 178503218, compound

HRID 724325Notes

Reaction equation

HRID 724325 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10](=[O:27])[C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[N:13][C:12]=2[O:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([S:25][CH3:26])[CH:20]=2)[CH2:5][CH2:4]1.C(N(CC)CC)C.[CH3:35][C:36]([CH3:41])([CH3:40])[C:37](O)=[O:38].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[CH3:35][C:36]([CH3:41])([CH3:40])[C:37]([NH:2][C@@H:3]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10](=[O:27])[C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[N:13][C:12]=2[O:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([S:25][CH3:26])[CH:20]=2)[CH2:5][CH2:4]1)=[O:38]

Participants

7

Reactant 5

HCID 6417Pivalic acidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178503208HCID 178503208, compound

Product 1

HCID 178503218HCID 178503218, compoundYield 100.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-(cis-4-Amino-cyclohexyl)-5-fluoro-2-(3-methylsulfanyl-phenoxy)-nicotinamide hydrochloride (100 mg, 0.243 mmol) was dissolved in dimethylformamide (1 ml) and triethylamine (100 μl, 0.729 mmol) was added followed by 2,2-dimethylpropionic acid (34 μl, 0.291 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (56 mg, 0.291 mmol) and 1-hydroxybenzotriazole (39 mg, 0.291 mmol). The reaction was stirred under nitrogen at room temperature for 64 h and the solvent was removed under reduced pressure. The residue was partitioned between sat. sodium bicarbonate solution (5 ml) and ethyl acetate (10 ml) and the aqueous phase was extracted with ethyl acetate (3×10 ml). The combined organic extracts were washed with water (2×5 ml), brine (5 ml), dried over MgSO4 and the solvent was removed under reduced pressure. The residue was triturated with diethylether (5 ml) to give N-[cis-4-(2,2-dimethylpropionylamino)-cyclohexyl]-5-fluoro-2-(3-methylsulfanyl-phenoxy)-nicotinamide (112 mg) as a white solid.

Workup

  1. customthe solvent was removed under reduced pressure
  2. customThe residue was partitioned between sat. sodium bicarbonate solution (5 ml) and ethyl acetate (10 ml)
  3. extractionthe aqueous phase was extracted with ethyl acetate (3×10 ml)
  4. washThe combined organic extracts were washed with water (2×5 ml), brine (5 ml)
  5. dry with materialdried over MgSO4
  6. customthe solvent was removed under reduced pressure
  7. customThe residue was triturated with diethylether (5 ml)

Sources & evidence

ORD record
ord-73c92a506711449d9941551c99c5fb45
Source dataset
uspto-grants-2006_11
Patent number
US07141586B2

Reaction notes

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