Sodium hydride → HCID 86686668, compound

HRID 334373Notes

Reaction equation

HRID 334373 reaction equation
[CH3:1][Si:2]([CH3:47])([CH3:46])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:45])([CH3:44])[CH3:43])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:21][CH:22]=3)=[C:12]2[N:11]=[C:10]([CH:29]2[CH2:34][CH2:33][C:32]([CH2:36]O)([OH:35])[CH2:31][CH2:30]2)[CH:9]=1.CS(Cl)(=O)=O.[CH3:53][S:54]([NH2:57])(=[O:56])=[O:55].[H-].[Na+].[NH4+].[Cl-]>C(Cl)Cl.CN(C=O)C.CCOC(C)=O>[CH3:44][Si:42]([CH3:45])([CH3:43])[CH2:41][CH2:40][O:39][CH2:38][N:7]([CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:46])([CH3:47])[CH3:1])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:21][CH:22]=3)=[C:12]2[N:11]=[C:10]([CH:29]2[CH2:34][CH2:33][C:32]([CH2:36][NH:57][S:54]([CH3:53])(=[O:56])=[O:55])([OH:35])[CH2:31][CH2:30]2)[CH:9]=1

Participants

9

Reactant 5

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 31297Methanesulfonyl chlorideHCID 72879MethanesulfonamideHCID 66583993HCID 66583993, compound

Product 1

HCID 86686668HCID 86686668, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanol (820 mg, 1.21 mmol) in DCM (10 mL) was added TEA (0.337 mL, 2.42 mmol), followed by MsCl (0.104 mL, 1.33 mmol) at 0° C. and stirred for 1 h. The reaction mixture was concentrated, and then dissolved in EtOAc, washed with H2O and brine, dried over Na2SO4, and concentrated to afford a pale yellow oil. This oil was dissolved in DMF (10 mL). MeSO2NH2 (1.5 eq) was added, followed by NaH (4.0 eq). The resulting reaction mixture was heated at 90° C. for 2 d. The reaction mixture was diluted with EtOAc, neutralized with NH4Cl, washed with H2O and brine, dried over Na2SO4, and concentrated. The crude product was purified by a SiO2 column (0-10% MeOH/DCM, Rf=0.65 in 10% MeOH/DCM) to afford N-((4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-hydroxycyclohexyl)methyl)methanesulfonamide as a brownish oil (594 mg). HPLC-MS TR=2.86 min (UV 254 nm, 10 min method); mass calculated for formula C37H56N6O5SSi2 752.4, observed LCMS m/z 753.1 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutiondissolved in EtOAc
  3. washwashed with H2O and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customto afford a pale yellow oil
  7. customThe resulting reaction mixture
  8. washwashed with H2O and brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customThe crude product was purified by a SiO2 column (0-10% MeOH/DCM, Rf=0.65 in 10% MeOH/DCM)

Sources & evidence

ORD record
ord-8cbb510fb1b9421eb0cfb1973873f68c
Source dataset
uspto-grants-2014_11
Patent number
US08883801B2

Reaction notes

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