Methanamine, N-methoxy-, hydrochloride (1:1) → tert-butyl 1-(methoxy(methyl)carbamoyl)-3-phenyl-5,6-dihydroimidazo[1,5-a]pyrazine-7(8H)-carboxylate

HRID 535949Notes

Reaction equation

HRID 535949 reaction equation
[C:1]1([C:7]2[N:11]3[CH2:12][CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][C:10]3=[C:9]([C:23](OC)=[O:24])[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH3:28][NH:29][O:30][CH3:31].C([Mg]Cl)(C)C>C1COCC1>[CH3:31][O:30][N:29]([CH3:28])[C:23]([C:9]1[N:8]=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:11]2[CH2:12][CH2:13][N:14]([C:16]([O:18][C:19]([CH3:21])([CH3:22])[CH3:20])=[O:17])[CH2:15][C:10]=12)=[O:24]

Participants

5

Reactant 3

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 576350867-tert-butyl 1-methyl 3-phenyl-5,6-dihydroimidazo[1,5-a]pyrazine-1,7(8H)-dicarboxylate2×HCID 178418918HCID 178418918, compound

Product 1

HCID 57635358tert-butyl 1-(methoxy(methyl)carbamoyl)-3-phenyl-5,6-dihydroimidazo[1,5-a]pyrazine-7(8H)-carboxylateYield 83.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

Under a nitrogen atmosphere 7-tert-butyl 1-methyl 3-phenyl-5,6-dihydroimidazo[1,5-a]pyrazine-1,7(8H)-dicarboxylate (Intermediate 3A) (1.50 g, 4.20 mmol) was dissolved in THF (6 mL) and N,O-dimethyl-hydroxylamine hydrochloride (1.23 g, 12.59 mmol) was added. The resulting suspension was cooled to −20° C. and a solution of iPrMgCl (2M, 6.3 mL, 12.59 mmol) in THF was added dropwise over 10 min. The mixture was stirred for 20 min at −10° C. and then was quenched with saturated aqueous NH4Cl. The mixture was extracted with EtOAc, dried over anhydrous Na2SO4, filtered and concentrated to provide Intermediate 26A as a white solid (1.35 g, 83%). 1H-NMR (400 MHz, CDCl3) δ: 1.52 (s, 9H), 3.63 (s, 3H), 3.80 (m, 2H), 3.90 (s, 3H), 4.12 (t, 2H), 5.02 (s, 2H), 7.46 (m, 3H), 7.65 (m, 2H); LCMS (+ESI) m/z 387.1 [M+H]+.

Workup

  1. customwas quenched with saturated aqueous NH4Cl
  2. extractionThe mixture was extracted with EtOAc
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d62aede38fbb4c43ba45aa14849c0194
Source dataset
uspto-grants-2014_10
Patent number
US08859538B2

Reaction notes

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