Diisopropylethylamine → US12358901, Example RE6

HRID 527718Notes

Reaction equation

HRID 527718 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]([CH3:50])([CH3:49])[C:45](OC)=[O:46]>C(Cl)Cl>[CH3:50][C:44]1([CH3:49])[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]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 13258034Methyl 2-aminoisobutyrate hydrochlorideHCID 679599396-(7-methylspiro[2H-benzofuran-3,1'-cyclopropane]-4-yl)oxypyridin-3-amine2×

Product 1

HCID 57411298US12358901, Example RE6

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of triphosgene (30 mg, 0.1 mmol) in dry DCM (1 ml) at CPC, 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 158, 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 2-amino-2-methylpropanoate hydrochloride (30 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-1432d31d85c140cb92997c21de76a858
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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