Acetic Anhydride → 1-((1S,4S)-5-(6-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-2-(2-azabicyclo[2.1.1]hexan-2-yl)pyrimidin-4-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)ethanone

HRID 1778176Notes

Reaction equation

HRID 1778176 reaction equation
[CH:1]12[CH2:6][CH:4]([CH2:5]1)[CH2:3][N:2]2[C:7]1[N:12]=[C:11]([C:13]2[CH:14]=[C:15]([C:20]([F:23])([F:22])[F:21])[C:16]([NH2:19])=[N:17][CH:18]=2)[CH:10]=[C:9]([N:24]2[CH2:29][C@@H:28]3[CH2:30][C@H:25]2[CH2:26][NH:27]3)[N:8]=1.[C:31](OC(=O)C)(=[O:33])[CH3:32].C(N(C(C)C)C(C)C)C>CS(C)=O>[NH2:19][C:16]1[N:17]=[CH:18][C:13]([C:11]2[N:12]=[C:7]([N:2]3[CH2:3][CH:4]4[CH2:5][CH:1]3[CH2:6]4)[N:8]=[C:9]([N:24]3[CH2:29][C@@H:28]4[CH2:30][C@H:25]3[CH2:26][N:27]4[C:31](=[O:33])[CH3:32])[CH:10]=2)=[CH:14][C:15]=1[C:20]([F:23])([F:22])[F:21]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 1176783475-(2-(2-azabicyclo[2.1.1]hexan-2-yl)-6-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)pyrimidin-4-yl)-3-(trifluoromethyl)pyridin-2-amine

Product 1

HCID 1176783221-((1S,4S)-5-(6-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-2-(2-azabicyclo[2.1.1]hexan-2-yl)pyrimidin-4-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)ethanoneYield 45.8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 5-(2-(2-azabicyclo[2.1.1]hexan-2-yl)-6-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)pyrimidin-4-yl)-3-(trifluoromethyl)pyridin-2-amine (80 mg, 0.22 mmol) in DMSO (2 mL) was added acetic anhydride (46 mg, 0.44 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.1 mL). The mixture was stirred at room temperature for 25 min. The mixture was concentrated in vacuum and the residue was purified by Prep-HPLC (BASE) to provide 1-((1S,4S)-5-(6-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-2-(2-azabicyclo[2.1.1]hexan-2-yl)pyrimidin-4-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)ethanone (46.34 mg, 40.0% yield). LCMS (ESI): [MH]+=459.9; 1H NMR (400 MHz, DMSO-d6) δ 8.91 (s, 1H), 8.36 (s, 1H), 6.79 (s, 2H), 6.53-6.21 (m, 1H), 5.10-4.89 (m, 1H), 4.80-4.78 (m, 1H), 4.74-4.63 (m, 1H), 3.55-3.51 (m, 1H), 3.44-3.35 (m, 2H), 3.23-2.84 (m, 4H), 2.82 (s, 1H), 2.00 (s, 1H), 1.91 (s, 3H), 1.83-1.81 (m, 2H), 1.29 (d, J=2.0 Hz, 2H).

Workup

  1. concentrationThe mixture was concentrated in vacuum
  2. customthe residue was purified by Prep-HPLC (BASE)

Sources & evidence

ORD record
ord-5d6772ee34a94f93b7b623ffd9883a88
Source dataset
uspto-grants-2016_02
Patent number
US09266862B2

Reaction notes

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