(Diethylamino)sulfur trifluoride → HCID 58292905, compound

HRID 511400Notes

Reaction equation

HRID 511400 reaction equation
O[CH:2]([P:31](=[O:38])([O:35][CH2:36][CH3:37])[O:32][CH2:33][CH3:34])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[N:15]=[C:14]([NH:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23](=[O:26])[NH:24][CH3:25])[C:13]([C:27]([F:30])([F:29])[F:28])=[CH:12][N:11]=2)=[CH:5][CH:4]=1.CCN(S(F)(F)[F:45])CC.C([O-])(O)=O.[Na+]>C(Cl)Cl>[F:45][CH:2]([P:31](=[O:38])([O:35][CH2:36][CH3:37])[O:32][CH2:33][CH3:34])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[N:15]=[C:14]([NH:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23](=[O:26])[NH:24][CH3:25])[C:13]([C:27]([F:30])([F:28])[F:29])=[CH:12][N:11]=2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 58292937HCID 58292937, compound

Product 1

HCID 58292905HCID 58292905, compoundYield 19.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of diethyl [hydroxy(4-{[4-{[2-(methylcarbamoyl)phenyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)methyl]phosphonate (Example 133, 8.00 mg, 0.014 mmol) and DAST (7 mg, 0.043 mmol) in DCM (3 mL) was stirred at 0° C. for 1 h. The was treated with sat. NaHCO3 (aq) (3 mL). The layers were separated and the aqueous layer was extracted with DCM (3×5 mL). The organic layers were combined, dried over MgSO4, filtered, concentrated, and residue was purified by prep TLC (5% 7 N ammonia in MeOH in DCM) to give 1.5 mg of the desired product (yield: 19%). 1H NMR (CD3OD, 400 MHz): δ=1.24 (t, J=7.6 Hz, 3 H), 1.32 (t, J=7.2 Hz, 3 H), 2.90 (s, 3 H), 4.00-4.17 (m, 4 H), 5.82 (dd, J=7.2, 44.0 Hz, 1 H), 7.20 (dt, J=1.2, 8.4 Hz, 1 H), 7.39 (d, J=8.4 Hz, 2 H), 7.50 (dt, J=2.0, 8.8 Hz, 1 H), 7.64 (dd, J=1.2, 8.0 Hz, 1 H), 7.69 (d, J=8.0 Hz, 2 H), 8.36 (s, 1 H), 8.43 (d, J=7.2 Hz. 1 H). MS (ES+): m/z 556.14 [MH+]. HPLC: tR=1.50 min (UPLC TOF, polar—3 min).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with DCM (3×5 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customresidue was purified by prep TLC (5% 7 N ammonia in MeOH in DCM)

Sources & evidence

ORD record
ord-f0526941db5343eaad0dbaf035ee3a0f
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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