Diisopropylethylamine → HCID 57989800, compound

HRID 1671099Notes

Reaction equation

HRID 1671099 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[N:10][C:9]=2[C:17]2[C:18]([F:35])=[C:19]([NH:23][S:24]([C:27]3[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=3[F:34])(=[O:26])=[O:25])[CH:20]=[CH:21][CH:22]=2)[CH:5]=[CH:4][N:3]=1.[NH2:36][CH2:37][CH2:38][N:39]1[CH2:43][CH2:42][CH2:41][C:40]1=[O:44].CCN(C(C)C)C(C)C>CO.C(Cl)Cl>[CH3:14][C:13]([C:11]1[S:12][C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:36][CH2:37][CH2:38][N:39]3[CH2:43][CH2:42][CH2:41][C:40]3=[O:44])[N:7]=2)=[C:9]([C:17]2[C:18]([F:35])=[C:19]([NH:23][S:24]([C:27]3[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=3[F:34])(=[O:26])=[O:25])[CH:20]=[CH:21][CH:22]=2)[N:10]=1)([CH3:16])[CH3:15]

Participants

6

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 906601-(2-Aminoethyl)pyrrolidin-2-oneHCID 44516823N-[3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl]-2,5-difluorobenzenesulfonamide

Product 1

HCID 57989800HCID 57989800, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,5-difluorobenzenesulfonamide (0.15 g, 0.28 mmol), 1-(2-aminoethyl)-2-pyrrolidinone (0.18 g, 0.83 mmol) and DIEA (0.10 ml, 0.56 mmol) in MeOH (0.5 ml) was heated at 50° C. for 2 h. LCMS analysis indicated that the reaction was proceeding very slowly, another equivalent amine and DIEA was added and the reaction was heated overnight. LCMS analysis indicated the reaction had still not progressed sufficiently so the reaction was heated overnight again. LCMS analysis indicated the reaction had progressed sufficiently so the reaction mixture was concentrated onto silica gel and purified by flash chromatography to afford a colourless foam. The product was dissolved in DCM and washed with HCl (10% Aq.) to remove some residual DIEA and the organics were dried over MgSO4, filtered and the filtrate was concentrated in vacuo to afford the title compound (0.12 g, 67% yield); 1H NMR (400 MHz, DMSO-d6) δ ppm 10.77 (s, 1H), 8.07 (d, J=5.1 Hz, 1H), 7.22-7.65 (m, 7H), 3.21-3.45 (m, 6H), 2.11-2.22 (m, 2H), 1.82-1.93 (m, 2H), 1.41 (s, 9H). MS (ES+): 631 [M+H]+.

Workup

  1. temperaturethe reaction was heated overnight
  2. temperaturewas heated overnight again
  3. concentrationwas concentrated onto silica gel
  4. custompurified by flash chromatography
  5. customto afford a colourless foam
  6. washwashed with HCl (10% Aq.)
  7. customto remove some residual DIEA
  8. dry with materialthe organics were dried over MgSO4
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-bec4653df96d48088a09b709a65bdc13
Source dataset
uspto-grants-2011_08
Patent number
US07994185B2

Reaction notes

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