Diisopropylethylamine → HCID 86697853, compound

HRID 2279914Notes

Reaction equation

HRID 2279914 reaction equation
Cl[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][P:21](=[O:29])([O:25][CH:26]([CH3:28])[CH3:27])[O:22][CH2:23][CH3:24])=[CH:16][C:15]=1[O:30][CH3:31].C(N(C(C)C)CC)(C)C>ClC(Cl)C.C(O)(C)(C)C.[Cl-].[Cl-].[Zn+2]>[Cl:8][C:6]1[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=[C:2]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([CH2:20][P:21](=[O:29])([O:25][CH:26]([CH3:28])[CH3:27])[O:22][CH2:23][CH3:24])=[CH:16][C:15]=2[O:30][CH3:31])[N:7]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 86697854HCID 86697854, compound2×

Product 1

HCID 86697853HCID 86697853, compound

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 63651,1-DichloroethaneSolvent2×HCID 6386tert-ButanolSolvent2×

Procedure

A solution of 2,4-dichloro-5-trifluoromethyl-pyrimidine (7.5 g, 34.7 mmol) in dichloroethane and t-butanol (1:1, 10 mL) was treated with ZnCl2 (1M solution in ether, 35 mL) and stirred for half an hour at RT. The reaction mixture was cooled to 0° C. and a solution of ethyl propan-2-yl [(4-amino-3-methoxyphenyl) methyl]phosphonate (Compound 72E, 5 g, 16.28 mmol) in dichloroethane and t-butanol (1:1, 10 mL) followed by diisopropylethylamine (6 mL, 34.7 mmol) were added drop wise while stirring was continued for 24 hrs. The resulting white precipitate was filtered. The solid was dissolved in dichloromethane, washed with water (2×50 mL), dried over magnesium sulfate, filtered and evaporated to give 6.3 g of pure required isomer. 1H NMR (400 MHz, CDCl3) δ 8.6 (s, 1H), 8.32 (d, J=8.4 Hz, 1H), 8.04 (s, 1H), 7.04 (s, 1H), 6.89 (d, J=8 Hz, 1H), 4.73-4.76 (m, 1H), 4.08-4.11 (m, 2H), 3.95 (s, 3H), 3.23 (d, J=21 Hz, 2H), 1.24-1.33 (9H).

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. additionwere added drop wise
  3. stirringwhile stirring
  4. filtrationThe resulting white precipitate was filtered
  5. dissolutionThe solid was dissolved in dichloromethane
  6. washwashed with water (2×50 mL)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customto give 6.3 g of pure required isomer

Sources & evidence

ORD record
ord-c09cad3041964ce7a0c929ce3ce3d269
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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