Hydrochloric Acid → HCID 22315160, compound

HRID 398701Notes

Reaction equation

HRID 398701 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:13]([CH2:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[C:14](O)=[O:15])[CH:6]=[CH:7][C:8]=1[S:9]([CH3:12])(=[O:11])=[O:10])#[N:2].C(Cl)(=O)C(Cl)=O.[NH2:29][C:30]1[CH:35]=[CH:34][N:33]=[CH:32][N:31]=1.C(N(CC)CC)C.Cl>C(Cl)Cl.CN(C)C=O.O.C(OCC)(=O)C>[C:1]([C:3]1[CH:4]=[C:5]([CH:13]([CH2:17][CH:18]2[CH2:19][CH2:20][CH2:21][CH2:22]2)[C:14]([NH:29][C:30]2[CH:35]=[CH:34][N:33]=[CH:32][N:31]=2)=[O:15])[CH:6]=[CH:7][C:8]=1[S:9]([CH3:12])(=[O:10])=[O:11])#[N:2]

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 689584-AminopyrimidineHCID 120694992-(3-Cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid

Product 1

HCID 22315160HCID 22315160, compoundYield 22.4%

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 75, 125 mg, 0.389 mmol) in methylene chloride (3 mL) was treated with N,N-dimethylformamide (1 drop) and then cooled to 0° C. The reaction mixture was then treated with oxalyl chloride (0.050 mL, 0.583 mmol). The resulting reaction mixture was allowed to warm to 25° C. where it was stirred for 1 h. The reaction mixture was then concentrated in vacuo. The resulting yellow gel was diluted with methylene chloride (2 mL) and then slowly added to a solution of 4-aminopyrimidine (56 mg, 0.583 mmol) and triethylamine (0.108 mL, 0.778 mmol) in N,N-dimethylformamide (3 mL). The resulting reaction mixture was stirred at 25° C. for 20 h. The reaction mixture was then diluted with water (25 mL), a 1N aqueous hydrochloric acid solution (5 mL), and ethyl acetate (25 mL). The layers were separated, and the organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 1/1 then 1/3 hexanes/ethyl acetate) afforded 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-pyrimidin-4-yl-propionamide (34.7 mg, 22%) as a pale yellow foam: mp 79-84° C. (foam to gel); EI-HRMS m/e calcd for C20H22N4O3S (M+) 398.1413, found 398.1411.

Workup

  1. customThe resulting reaction mixture
  2. temperatureto warm to 25° C. where it
  3. concentrationThe reaction mixture was then concentrated in vacuo
  4. additionThe resulting yellow gel was diluted with methylene chloride (2 mL)
  5. customThe resulting reaction mixture
  6. stirringwas stirred at 25° C. for 20 h
  7. customThe layers were separated
  8. dry with materialthe organic layer was dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a162438f58f843ceb30ceb0a34b01447
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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