Methylamine → HCID 66628412, compound

HRID 2200979Notes

Reaction equation

HRID 2200979 reaction equation
[NH2:1][C:2]1[N:31]=[C:5]2[N:6]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[C:7]([CH3:20])=[C:8]([C:18]#[N:19])[C@@H:9]([C:10]3[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][CH:11]=3)[N:4]2[N:3]=1.ClC(OC1C=CC([N+]([O-])=O)=CC=1)=[O:34].[CH2:45]([N:47]([CH2:50]C)CC)C.CN>CN(C1C=CN=CC=1)C.C1COCC1.ClCCl>[C:18]([C:8]1[C@@H:9]([C:10]2[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][CH:11]=2)[N:4]2[N:3]=[C:2]([NH:1][C:45]([NH:47][CH3:50])=[O:34])[N:31]=[C:5]2[N:6]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:28])([F:30])[F:29])[CH:22]=2)[C:7]=1[CH3:20])#[N:19]

Participants

8

Reactant 4

HCID 6329Methylamine2×HCID 8471TriethylamineHCID 821294-Nitrophenyl chloroformateHCID 66627900HCID 66627900, compound

Product 1

HCID 66628412HCID 66628412, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Under an atmosphere of argon protective gas, (7R)-2-amino-7-(4-cyanophenyl)-5-methyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile (13 mg, 28 μmol) was initially charged in abs. dichloromethane (2 ml). At −78° C., 4-nitrophenyl chloroformate (28.6 mg, 142 μmol, 5 eq.), triethylamine (14.7 mg, 145 μmol, 5.1 eq.) and DMAP (3.5 mg, 28 μmol) were added. After 2 h of stirring at −78° C., the reaction mixture was allowed to thaw initially to −20° C. (2 h) and then to 0° C. (2 h). The mixture was then once more cooled to −78° C., and a 2 M solution of methylamine in THF (102 μl, 7.2 eq.) was added. The mixture was then warmed to −10° C. and stirred overnight. A 2 M solution of methylamine in THF (1 ml) was then added, the reaction mixture was concentrated under reduced pressure and the residue was purified by preparative HPLC (Reprosil C18 column, 30×250 mm; mobile phase: acetonitrile-water-0.1% TFA). After lyophilization, the product was obtained as a solid (5.9 mg, 43% of theory).

Workup

  1. customthaw initially to −20° C. (2 h)
  2. customto 0° C.
  3. custom(2 h)
  4. temperatureThe mixture was then once more cooled to −78° C.
  5. temperatureThe mixture was then warmed to −10° C.
  6. stirringstirred overnight
  7. concentrationthe reaction mixture was concentrated under reduced pressure
  8. customthe residue was purified by preparative HPLC (Reprosil C18 column, 30×250 mm; mobile phase: acetonitrile-water-0.1% TFA)
  9. customAfter lyophilization, the product was obtained as a solid (5.9 mg, 43% of theory)

Sources & evidence

ORD record
ord-90fc1bdbc52f4b268258c5bc70c933d2
Source dataset
uspto-grants-2016_06
Patent number
US09359362B2

Reaction notes

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