Methanesulfonyl chloride → HCID 57961732, compound

HRID 541770Notes

Reaction equation

HRID 541770 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:10]=[N:11][C:12]2[NH:13][C:14]3[CH:15]=[CH:16][CH:17]=[C:18]([CH:32]=3)[CH2:19][CH2:20][C:21]3[CH:29]=[C:25]([NH:26][C:27]=1[N:28]=2)[CH:24]=[C:23]([CH2:30]O)[CH:22]=3.CS(Cl)(=O)=O.C(N(CC)C(C)C)(C)C.[C:47]([O:51][C:52]([N:54]1[CH2:59][CH2:58][NH:57][CH2:56][CH2:55]1)=[O:53])([CH3:50])([CH3:49])[CH3:48]>C1COCC1.CN(C=O)C.Cl.C(OCC)(=O)C>[Cl:8][C:9]1[CH:10]=[N:11][C:12]2[NH:13][C:14]3[CH:15]=[CH:16][CH:17]=[C:18]([CH:32]=3)[CH2:19][CH2:20][C:21]3[CH:29]=[C:25]([NH:26][C:27]=1[N:28]=2)[CH:24]=[C:23]([CH2:30][N:57]1[CH2:56][CH2:55][N:54]([C:52]([O:51][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:53])[CH2:59][CH2:58]1)[CH:22]=3

Participants

9

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 81531Diisopropylethylamine2×HCID 143452tert-Butyl piperazine-1-carboxylateHCID 66896816HCID 66896816, compound

Product 1

HCID 57961732HCID 57961732, compoundYield 50.4%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of [6-chloro-2,4,8,22-tetraazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaen-11-yl]methanol trifluoroacetate (0.731 g, 1.56 mmol) in THF (15 mL) was added methanesulfonyl chloride (151 μL, 1.95 mmol) and N,N-diisopropylethylamine (0.93 mL, 5.32 mmol) at 0° C. The resulting reaction solution was stirred at same temperature for 2 hours. The reaction solution was diluted with DMF (8 mL) and N-tert-butoxycarbonylpiperazine (396 mg, 2.13 mmol) was added, followed by N,N-diisopropylethylamine (0.818 mL, 4.70 mmol). The reaction solution was stirred at 40° C. overnight. The reaction solution was diluted with 1 N HCl solution and ethyl acetate and the aqueous layer was extracted with ethyl acetate once. The aqueous layer was neutralized with 50% NaOH solution to pH 10, and then extracted with EtOAc twice. The combined organic solutions were dried over sodium sulfate, filtered and concentrated. The residue was purified by flash column chromatography to yield the desired product (410 mg, 50%). LCMS calculated for C28H34ClN6O2(M+H)+: m/z=521.2.

Workup

  1. customThe resulting reaction solution
  2. additionwas added
  3. stirringThe reaction solution was stirred at 40° C. overnight
  4. extractionthe aqueous layer was extracted with ethyl acetate once
  5. extractionextracted with EtOAc twice
  6. dry with materialThe combined organic solutions were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-3fce76274e6c4fc2a50357a09a16c138
Source dataset
uspto-grants-2014_10
Patent number
US08871753B2

Reaction notes

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