Methylamine → HCID 53473322, compound

HRID 2037449Notes

Reaction equation

HRID 2037449 reaction equation
CN.C1N=[CH:6][N:5]([C:8]([N:10]2C=N[CH:12]=[CH:11]2)=[O:9])C=1.CCN(C(C)C)C(C)C.NCC[C@@:27]1([C:50]2[CH:55]=[CH:54][C:53]([F:56])=[CH:52][CH:51]=2)[O:32][C:31](=[O:33])[N:30]([C@H:34]([C:36]2[CH:41]=[CH:40][C:39]([C:42]3[CH:47]=[CH:46][C:45]([F:48])=[CH:44][C:43]=3[F:49])=[CH:38][CH:37]=2)[CH3:35])[CH2:29][CH2:28]1>C(Cl)Cl>[F:49][C:43]1[CH:44]=[C:45]([F:48])[CH:46]=[CH:47][C:42]=1[C:39]1[CH:40]=[CH:41][C:36]([C@@H:34]([N:30]2[CH2:29][CH2:28][C@:27]([CH2:12][CH2:11][NH:10][C:8]([NH:5][CH3:6])=[O:9])([C:50]3[CH:51]=[CH:52][C:53]([F:56])=[CH:54][CH:55]=3)[O:32][C:31]2=[O:33])[CH3:35])=[CH:37][CH:38]=1

Participants

6

Reactant 4

HCID 6329MethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 53473235HCID 53473235, compound

Product 1

HCID 53473322HCID 53473322, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of methylamine (11 mg, 0.11 mmol) and CDI (20 mg, 0.13 mmol) in anhydrous CH2Cl2 (3 mL) was added DIEA (130 mg, 1.00 mmol) at 0° C. under nitrogen. The resulting mixture was stirred at ambient temperature for 1 h. (R)-6-(2-aminoethyl)-3-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one (40 mg, 0.088 mmol) was added to the above mixture, and the mixture was stirred at rt overnight. The mixture was concentrated in vacuo to give a residue, which was purified by preparative HPLC to afford 1-(2-((R)-3-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)ethyl)-3-methylurea (5 mg, 12%). 1H NMR (CDCl3): 1.56 (m, 3H), 2.10-2.30 (m, 4H), 2.35 (m, 1H), 2.75 (s, 3H), 3.01 (m, 1H), 3.09 (m, 1H), 3.30 (m, 1H), 5.69 (m, 1H), 6.86-6.96 (m, 2H), 7.08 (m, 4H), 7.25 (m, 2H), 7.30 (m, 3H).

Workup

  1. additionwas added to the above mixture
  2. concentrationThe mixture was concentrated in vacuo
  3. customto give a residue, which
  4. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-6780f2b53ff14c43927cdf5155230e85
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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