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 2278338Notes

Reaction equation

HRID 2278338 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 sane 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-27522d2bfec545d6a9ed31361116029f
Source dataset
uspto-grants-2015_09
Patent number
US09133175B2

Reaction notes

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