Trifluoroacetic acid → N1-{2-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-5-pyrimidinyl}-3-methyl-D-valinamide

HRID 527561Notes

Reaction equation

HRID 527561 reaction equation
[CH3:1][C:2]1([CH3:34])[C:6]2[C:7]([O:11][C:12]3[N:17]=[CH:16][C:15]([NH:18][C:19]([C@H:21]([NH:26]C(=O)OC(C)(C)C)[C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[CH:14][N:13]=3)=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3]1.C(O)(C(F)(F)F)=O>ClCCl>[CH3:1][C:2]1([CH3:34])[C:6]2[C:7]([O:11][C:12]3[N:17]=[CH:16][C:15]([NH:18][C:19](=[O:20])[C@@H:21]([C:22]([CH3:25])([CH3:24])[CH3:23])[NH2:26])=[CH:14][N:13]=3)=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 679669581,1-dimethylethyl {(1R)-1-[({2-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-5-pyrimidinyl}amino)carbonyl]-2,2-dimethylpropyl}carbamate2×

Product 1

HCID 86698429N1-{2-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-5-pyrimidinyl}-3-methyl-D-valinamideYield 106.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1,1-dimethylethyl {(1R)-1-[({2-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-5-pyrimidinyl}amino)carbonyl]-2,2-dimethylpropyl}carbamate (Intermediate 77, 13 mg) in dry dichloromethane (0.5 ml) cooled to 0° C., TFA (85 μl, 1.105 mmol) was added dropwise and the solution was stirred for 3 hours at that temperature. The volatiles were evaporated. The residue was dissolved with dichloromethane (2 ml) and an aqueous saturated solution of NaHCO3 was added (4 ml). The layers were separated and the aqueous layer was extracted twice with dichloromethane. The gathered organic layers were dried over sodium sulphate and evaporated to afford the title compound (10.9 mg).

Workup

  1. customThe volatiles were evaporated
  2. dissolutionThe residue was dissolved with dichloromethane (2 ml)
  3. additionan aqueous saturated solution of NaHCO3 was added (4 ml)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted twice with dichloromethane
  6. dry with materialThe gathered organic layers were dried over sodium sulphate
  7. customevaporated

Sources & evidence

ORD record
ord-daf656a1807046a58cfd02fcb5bf650f
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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