Cyanuric chloride → HCID 42628061, compound

HRID 1162626Notes

Reaction equation

HRID 1162626 reaction equation
N1C(Cl)=NC(Cl)=NC=1Cl.CN1CCOCC1.[Cl:17][C:18]1[S:22][C:21]([C:23]([NH:25][C@H:26]2[CH2:30][N:29]([CH2:31][C:32](=[O:48])[NH:33][C:34]3[CH:39]=[CH:38][C:37]([N:40]4[CH:45]=[CH:44][CH:43]=[CH:42][C:41]4=[O:46])=[CH:36][C:35]=3[F:47])[C@H:28]([C:49](O)=[O:50])[CH2:27]2)=[O:24])=[CH:20][CH:19]=1>COCCOC>[F:47][C:35]1[CH:36]=[C:37]([N:40]2[CH:45]=[CH:44][CH:43]=[CH:42][C:41]2=[O:46])[CH:38]=[CH:39][C:34]=1[NH:33][C:32]([CH2:31][N:29]1[C@H:28]([CH2:49][OH:50])[CH2:27][C@@H:26]([NH:25][C:23]([C:21]2[S:22][C:18]([Cl:17])=[CH:19][CH:20]=2)=[O:24])[CH2:30]1)=[O:48]

Participants

5

Reactant 3

HCID 7954Cyanuric chlorideHCID 79724-MethylmorpholineHCID 58748169HCID 58748169, compound

Product 1

HCID 42628061HCID 42628061, compoundYield 13.7%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 44 mg cyanuric chloride in 1.5 ml 1,2-dimethoxyethane were added 0.03 ml N-methylmorpholine. The resulting white suspension was treated with 150 mg (2S,4R)-4-[(5-chloro-thiophene-2-carbonyl)-amino]-1-{[2-fluoro-4-(2-oxo-pyridin-1-yl)-phenylcarbamoyl]-methyl}-pyrrolidine-2-carboxylic acid (example 12) in 0.5 ml 1,2-dimethoxyethane and stirred at r.t for 3 hrs. The precipitate was filtered off. The filtrate was cooled to 0° C. A solution of 13 mg NaBH4 in 0.7 ml H2O was added dropwise. The mixture was stirred for 5 min at 0° C., then diluted with water and extracted with EtOAc. The organic layer was washed with water, dried over MgSO4, filtrated and concentrated. The crude product was purified by chromatography (silica gel; gradient: CH2Cl2->CH2Cl2/MeOH 9:1) to give 20 mg 5-chloro-thiophene-2-carboxylic acid ((3R,5S)-1-{[2-fluoro-4-(2-oxo-pyridin-1-yl)-phenylcarbamoyl]-methyl}-5-hydroxymethyl-pyrrolidin-3-yl)-amide. White solid. MS 505.4 ([M+H]+)

Workup

  1. filtrationThe precipitate was filtered off
  2. additionA solution of 13 mg NaBH4 in 0.7 ml H2O was added dropwise
  3. stirringThe mixture was stirred for 5 min at 0° C.
  4. additiondiluted with water
  5. extractionextracted with EtOAc
  6. washThe organic layer was washed with water
  7. dry with materialdried over MgSO4
  8. filtrationfiltrated
  9. concentrationconcentrated
  10. customThe crude product was purified by chromatography (silica gel; gradient: CH2Cl2->CH2Cl2/MeOH 9:1)

Sources & evidence

ORD record
ord-5421f5a22d0e4e2cae5f6bf64d9b396f
Source dataset
uspto-grants-2010_10
Patent number
US07820699B2

Reaction notes

Loading…