Acetonitrile → Iminodicarbonsaure

HRID 596017Notes

Reaction equation

HRID 596017 reaction equation
[NH2:1][C:2]1[C:3]([C:15]2[CH:27]=[CH:26][C:18]([C:19]([O:21]C(C)(C)C)=[O:20])=[C:17]([F:28])[CH:16]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:6][N:7]=1.CC([O:33][C:34]([O:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=O)(C)C.C(#[N:46])C>CN(C1C=CN=CC=1)C>[C:34]([NH:46][C:19]([OH:21])=[O:20])([OH:36])=[O:33].[C:40]([O:39][C:37]([NH:1][C:2]1[C:3]([C:15]2[CH:27]=[CH:26][C:18]([C:19]([O-:21])=[O:20])=[C:17]([F:28])[CH:16]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:6][N:7]=1)=[O:38])([CH3:41])([CH3:42])[CH3:43]

Participants

6

Reactant 3

HCID 6342AcetonitrileHCID 90495Di-tert-butyl dicarbonateHCID 118045455Tert-butyl 4-(3-amino-6-(4-oxocyclohexyl)pyrazin-2-yl)-2-fluorobenzoate

Product 2

HCID 13267551IminodicarbonsaureHCID 1317346144-(3-((Tert-butoxycarbonyl)amino)-6-(4-oxocyclohexyl)pyrazin-2-yl)-2-fluorobenzoate

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

To a solution of tert-butyl 4-(3-amino-6-(4-oxocyclohexyl)pyrazin-2-yl)-2-fluorobenzoate (3 g, 7.78 mmol) in acetonitrile (130 mL) was added Boc2O (6.33 mL, 27.2 mmol) and DMAP (0.048 g, 0.389 mmol). The reaction mixture was stirred overnight at room temperature. After volatile materials were removed on rotavap under reduced pressure, the crude product was purified by flash chromatography eluting with 0-50% of EtOAc/heptane to provide imidodicarbonic acid, 4-(3-((tert-butoxycarbonyl)amino)-6-(4-oxocyclohexyl)pyrazin-2-yl)-2-fluorobenzoate, 1,3-bis(1,1-dimethylethyl) ester (4.34 g, 7.41 mmol, 95%). LCMS (m/z): 586.5 (MH+), 1.24 min; 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.52-8.41 (m, 1H), 7.97 (t, J=7.7 Hz, 1H), 7.61-7.44 (m, 2H), 3.46-3.30 (m, 1H), 2.68-2.52 (m, 4H), 2.38 (dd, J=3.0, 13.7 Hz, 2H), 2.28-2.10 (m, 2H), 1.69-1.61 (m, 9H), 1.42-1.29 (m, 18H).

Workup

  1. customAfter volatile materials were removed on rotavap under reduced pressure
  2. customthe crude product was purified by flash chromatography
  3. washeluting with 0-50% of EtOAc/heptane

Sources & evidence

ORD record
ord-86e82dabe5a84bb0b2390972d3e42716
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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