Diisopropylethylamine → HCID 86708621, compound

HRID 921737Notes

Reaction equation

HRID 921737 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][N:5]([C:8]2[C:9]([Cl:31])=[C:10]([NH:16][C:17]3[N:22]=[C:21]([NH:23][CH2:24][CH3:25])[C:20]4=[N:26][CH:27]=[C:28]([C:29]#[N:30])[N:19]4[N:18]=3)[CH:11]=[C:12]([C:14]#[N:15])[CH:13]=2)[CH2:4][C@H:3]1[OH:32].CCN(C(C)C)C(C)C.[C:42](Cl)(=O)[O:43]C1C=CC([N+]([O-])=O)=CC=1>C(O)CO.C1COCC1.CCOC(C)=O>[Cl:31][C:9]1[C:8]([N:5]2[CH2:6][CH2:7][C@H:2]3[NH:1][C:42](=[O:43])[O:32][C@@H:3]3[CH2:4]2)=[CH:13][C:12]([C:14]#[N:15])=[CH:11][C:10]=1[NH:16][C:17]1[N:22]=[C:21]([NH:23][CH2:24][CH3:25])[C:20]2=[N:26][CH:27]=[C:28]([C:29]#[N:30])[N:19]2[N:18]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformateHCID 86708622HCID 86708622, compound

Product 1

HCID 86708621HCID 86708621, compoundYield 19%

Reagents, catalysts & solvents 3

HCID 174Ethylene GlycolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-((3-((3R,4R)-4-amino-3-hydroxypiperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (30 mg, 0.066 mmol) and DIPEA (0.035 mL, 0.199 mmol) in ethane-1,2-diol 1 mL at 0° C. (ice bath) was treated with 4-nitrophenyl carbonochloridate (18 mg, 0.089 mmol). The reaction was stirred for 0.5 hour and the reaction is complete. The reaction mixture was diluted with THF 1 ml/EtOAc 30 ml, washed 2× brine (5 ml) and dried over Na2SO4. The solvents removed and the crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×200 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: water with 20-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile: water with 20-mM ammonium acetate; Gradient: 35-80% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to afford 2-((2-chloro-5-cyano-3-((3aR,7aR)-2-oxohexahydrooxazolo[5,4-c]pyridin-5(2H)-yl)phenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (6.0 mg).

Workup

  1. washwashed 2× brine (5 ml)
  2. dry with materialdried over Na2SO4
  3. customThe solvents removed
  4. customthe crude material was purified via preparative LC/MS with the following conditions
  5. waitGradient: 35-80% B over 25 minutes
  6. customa 5-minute hold
  7. additionFractions containing the desired product
  8. customdried via centrifugal evaporation

Sources & evidence

ORD record
ord-9bfa47a3e63447e8b21567e39191dd47
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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