(Diethylamino)sulfur trifluoride → HCID 58292905, compound

HRID 1947970Notes

Reaction equation

HRID 1947970 reaction equation
[CH2:1]([O:3][P:4]([CH:9](O)[C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21]([NH:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30](=[O:33])[NH:31][CH3:32])[C:20]([C:34]([F:37])([F:36])[F:35])=[CH:19][N:18]=2)=[CH:12][CH:11]=1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].CCN(S(F)(F)[F:45])CC.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:1]([O:3][P:4]([CH:9]([F:45])[C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21]([NH:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30](=[O:33])[NH:31][CH3:32])[C:20]([C:34]([F:35])([F:37])[F:36])=[CH:19][N:18]=2)=[CH:12][CH:11]=1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2]

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, 3H), 1.32 (t, J=7.2 Hz, 3H), 2.90 (s, 3H), 4.00-4.17 (m, 4H), 5.82 (dd, J=7.2, 44.0 Hz, 1H), 7.20 (dt, J=1.2, 8.4 Hz, 1H), 7.39 (d, J=8.4 Hz, 2H), 7.50 (dt, J=2.0, 8.8 Hz, 1H), 7.64 (dd, J=1.2, 8.0 Hz, 1H), 7.69 (d, J=8.0 Hz, 2H), 8.36 (s, 1H), 8.43 (d, J=7.2 Hz, 1H). 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-d5f2245c1e864bb0824a0f299184ecb0
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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