Trifluoroacetic acid → HCID 49821674, compound

HRID 1947827Notes

Reaction equation

HRID 1947827 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([Cl:19])=[CH:4][N:3]=1.[CH2:20]([O:22][P:23]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=1)(=[O:27])[O:24][CH2:25][CH3:26])[CH3:21].C(O)(C(F)(F)F)=O>>[CH2:25]([O:24][P:23]([CH2:28][C:29]1[CH:30]=[CH:31][C:32]([NH:35][C:2]2[N:7]=[C:6]([NH:8][C:9]3[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=3[C:11](=[O:12])[NH:13][CH3:14])[C:5]([Cl:19])=[CH:4][N:3]=2)=[CH:33][CH:34]=1)(=[O:27])[O:22][CH2:20][CH3:21])[CH3:26]

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 88358Diethyl p-aminobenzylphosphonateHCID 579741322-(2,5-Dichloropyrimidin-4-ylamino)-N-methylbenzamide

Product 1

HCID 49821674HCID 49821674, compoundYield 24%

Procedure

A solution of 2-[(2,5-dichloropyrimidin-4-yl)amino]-N-methylbenzamide (29.7 mg, 0.100 mmol), diethyl(4-aminobenzyl)phosphonate (29.2 mg, 0.120 mmol), TFA (23 uL, 0.30 mmol) and TFE (1.0 mL) was heated at 100° C. for 30 minutes in a microwave reactor. The reaction mixture was then quenched with saturated aqueous sodium bicarbonate (15 mL) and extracted with EtOAc (20 mL). The organic layer was washed with brine (15 mL), dried over anhydrous NaSO4, filtered, and concentrated in vacuo to yield a yellow solid. This material was purified by preparative HPLC (MDP) to afford 12 mg of diethyl{4-[(5-chloro-4-{[2-(methylcarbamoyl)phenyl]amino}pyrimidin-2-yl)amino]benzyl}phosphonate (yield: 24%). 1H NMR (CD3OD, 400 MHz): δ=1.26 (t, J=7.07 Hz, 6H), 2.92 (s, 3H), 3.15-3.24 (m, 2H), 3.99-4.08 (m, 4H), 7.12 (td, J=7.64, 1.14 Hz, 1H), 7.21 (dd, J=8.59, 2.53 Hz, 2H), 7.48 (ddd, J=8.53, 7.26, 1.64 Hz, 1H), 7.55 (d, J=8.08 Hz, 2H), 7.65 (dd, J=7.83, 1.52 Hz, 1H), 8.06 (s, 1H), 8.70 (d, J=8.34 Hz, 1H). MS (ES+): m/z 506.15 [MH+] (TOF, polar).

Workup

  1. customThe reaction mixture was then quenched with saturated aqueous sodium bicarbonate (15 mL)
  2. extractionextracted with EtOAc (20 mL)
  3. washThe organic layer was washed with brine (15 mL)
  4. dry with materialdried over anhydrous NaSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto yield a yellow solid
  8. customThis material was purified by preparative HPLC (MDP)

Sources & evidence

ORD record
ord-e57ce9c08b2347beb26a83a5f1857de2
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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