Diisopropylethylamine → (5R)-5-ethyl-5-methyl-3-[6-(7-methylspiro[2H-benzofuran-3,1'-cyclopropane]-4-yl)oxy-3-pyridyl]imidazolidine-2,4-dione

HRID 1484666Notes

Reaction equation

HRID 1484666 reaction equation
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.CCN(C(C)C)C(C)C.[CH3:22][C:23]1[C:28]2[O:29][CH2:30][C:31]3([CH2:33][CH2:32]3)[C:27]=2[C:26]([O:34][C:35]2[N:40]=[CH:39][C:38]([NH2:41])=[CH:37][CH:36]=2)=[CH:25][CH:24]=1.Cl.[NH2:43][C@:44]([CH3:51])([CH2:49][CH3:50])[C:45](OC)=[O:46]>C(Cl)Cl>[CH2:49]([C@@:44]1([CH3:51])[NH:43][C:2](=[O:4])[N:41]([C:38]2[CH:39]=[N:40][C:35]([O:34][C:26]3[C:27]4[C:31]5([CH2:30][O:29][C:28]=4[C:23]([CH3:22])=[CH:24][CH:25]=3)[CH2:33][CH2:32]5)=[CH:36][CH:37]=2)[C:45]1=[O:46])[CH3:50]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 13018906(R)-2-Amino-2-methyl-butyric acid methyl ester hydrochlorideHCID 679599396-(7-methylspiro[2H-benzofuran-3,1'-cyclopropane]-4-yl)oxypyridin-3-amine2×

Product 1

HCID 57411182(5R)-5-ethyl-5-methyl-3-[6-(7-methylspiro[2H-benzofuran-3,1'-cyclopropane]-4-yl)oxy-3-pyridyl]imidazolidine-2,4-dione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of triphosgene (30 mg, 0.1 mmol) in dry DCM (1 ml) at 0° C., under nitrogen atmosphere, DIPEA (0.175 ml, 1.0 mmol) was added followed by the addition (slowly added) of a solution of 6-(7-methylspiro[2H-benzofuran-3,1′-cyclopropane]-4-yl)oxypyridin-3-amine (Intermediate 15, 27 mg, 0.1 mmol) in dry DCM (2 ml) and the reaction mixture was stirred for 15 minutes at the same temperature. After that a solution of Methyl (R)-2-amino-2-methyl-butyrate hydrochloride (33 mg, 0.2 mmol) in dry DCM (2 ml) was added and the reaction mixture was stirred for 30 minutes at 0° C. The reaction was quenched with a 1M aqueous solution of HCl (5 ml), diluted with DCM (10 ml) and two phases were separated. The organic layer was washed with brine (10 ml), dried (Na2SO4), filtered and evaporated affording the urea intermediate as yellow foam.

Workup

  1. additionfollowed by the addition (
  2. stirringthe reaction mixture was stirred for 30 minutes at 0° C
  3. customThe reaction was quenched with a 1M aqueous solution of HCl (5 ml)
  4. additiondiluted with DCM (10 ml) and two phases
  5. customwere separated
  6. washThe organic layer was washed with brine (10 ml)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated

Sources & evidence

ORD record
ord-df4d3377c26546e39ea620de6b388462
Source dataset
uspto-grants-2016_08
Patent number
US09422272B2

Reaction notes

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