Dichloromethane → HCID 67485888, compound

HRID 1430986Notes

Reaction equation

HRID 1430986 reaction equation
C([O:3][P:4]([CH2:9][C:10]1[CH:11]=[N:12][C:13]([NH:16][C:17](=[O:36])[C:18]2[CH:23]=[C:22]([O:24][CH2:25][CH2:26][C:27]3[CH:31]=[CH:30][S:29][CH:28]=3)[CH:21]=[C:20]([O:32][CH:33]([CH3:35])[CH3:34])[CH:19]=2)=[CH:14][CH:15]=1)(=[O:8])[O:5]CC)C.C[Si](Br)(C)C.C(Cl)[Cl:43]>>[ClH:43].[CH:33]([O:32][C:20]1[CH:19]=[C:18]([CH:23]=[C:22]([O:24][CH2:25][CH2:26][C:27]2[CH:31]=[CH:30][S:29][CH:28]=2)[CH:21]=1)[C:17]([NH:16][C:13]1[N:12]=[CH:11][C:10]([CH2:9][P:4](=[O:3])([OH:8])[OH:5])=[CH:15][CH:14]=1)=[O:36])([CH3:35])[CH3:34]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 76113BromotrimethylsilaneHCID 58528960HCID 58528960, compound

Product 1

HCID 67485888HCID 67485888, compoundYield 21.6%

Conditions

Temperature
-78 °C

Procedure

{6-[3-Isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoylamino]-pyridin-3-ylmethyl}-phosphonic acid diethyl ester (86.0 mg, 0.166 mmol) was dissolved in DCM (0.8 mL) and cooled to −78° C. TMSBr (0.21 mL, 1.61 mmol) was added and the reaction mixture was allowed to warm to rt over 24 hours. The reaction mixture was concentrated under reduced pressure and partitioned in diethyl ether (5 mL) and 1N aqueous sodium hydroxide (5 mL). The aqueous layer was rinsed twice with diethyl ether (5 mL), then acidified to pH=1 with concentrated hydrochloric acid and extracted with EtOAc (3×5 mL). The organic layer dried over sodium sulfate, filtered, and concentrated to give the title compound, {6-[3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoylamino]-pyridin-3-ylmethyl}-phosphonic acid hydrochloride (16.6 mg, 21.6% yield), as a pale brown foam. 1H NMR (300 MHz, DMSO-d6): δ 10.70 (s, 1H), 8.20 (s, 1H), 8.05 (d, J=6.0 Hz, 1H), 7.70 (d, J=6.0 Hz, 1H), 7.45 (d, 3.0 Hz, 1H), 7.30 (s, 1H), 7.20 (s, 1H), 7.15 (s, 1H), 7.10 (d, J=3.0 Hz, 1H), 6.65 (s, 1H), 4.70 (m, 1H), 4.25 (t, 2H), 3.10 (t, 2H), 2.95 (d, J=12.0 Hz, 2H), 1.25 (s, 6H); LCMS (m/z): 477.1 [C22H25N2O6PS+H] Anal. Calcd. for (C22H25N2O6PS+1.2 HCl): C, 50.79; H, 5.08; N, 5.38. Found: C, 50.72; H, 4.91; N, 4.80.

Workup

  1. temperatureto warm to rt over 24 hours
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. custompartitioned in diethyl ether (5 mL)
  4. washThe aqueous layer was rinsed twice with diethyl ether (5 mL)
  5. extractionextracted with EtOAc (3×5 mL)
  6. dry with materialThe organic layer dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-6cdc7790f49b44718b15dfa133878c42
Source dataset
uspto-grants-2015_01
Patent number
US08940927B2

Reaction notes

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