Methanol → HCID 86708604, compound

HRID 1430902Notes

Reaction equation

HRID 1430902 reaction equation
[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][CH:11]([NH:14][CH:15]3[CH2:18][O:17][CH2:16]3)[CH2:10][CH2:9]2)=[CH:6][C:5]([C:19]#[N:20])=[CH:4][C:3]=1[NH:21][C:22]1[N:27]=[C:26]([NH:28][CH2:29][CH3:30])[C:25]2=[N:31][CH:32]=[C:33]([C:34]#[N:35])[N:24]2[N:23]=1.C1[CH2:40][O:39][CH2:38]C1.CCN(C(C)C)C(C)C.C[OH:51]>CCOC(C)=O>[Cl:1][C:2]1[C:3]([NH:21][C:22]2[N:27]=[C:26]([NH:28][CH2:29][CH3:30])[C:25]3=[N:31][CH:32]=[C:33]([C:34]#[N:35])[N:24]3[N:23]=2)=[CH:4][C:5]([C:19]#[N:20])=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH:15]2[CH2:18][O:17][CH2:16]2)[C:38](=[O:51])[O:39][CH3:40])[CH2:10][CH2:9]1

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 86708603HCID 86708603, compound

Product 1

HCID 86708604HCID 86708604, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

2-((2-chloro-5-cyano-3-(4-(oxetan-3-ylamino)piperidin-1-yl)phenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 363) (20 mg, 0.041 mmol) in MeOH (6 mL)/THF (3 mL) at 0° C. (ice bath) was added DIPEA (21.26 μl, 0.122 mmol) and methyl carbonochloride [(60 μl, 0.775 mmol) total 3× (20 μl, 0.258 mmol) portions]. The reaction stirred at 25° C. for 30 min and the mixture was diluted with EtOAc, washed with sat'd NaHCO3 and brine. The organic layer was dried over Na2SO4 and concentrated. 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: 40-80% B over 20 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 methyl (1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)(oxetan-3-yl)carbamate (5.8 mg).

Workup

  1. washwashed with sat'd NaHCO3 and brine
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated
  4. customThe crude material was purified via preparative LC/MS with the following conditions
  5. waitGradient: 40-80% B over 20 minutes
  6. customa 5-minute hold
  7. additionFractions containing the desired product
  8. customdried via centrifugal evaporation

Sources & evidence

ORD record
ord-ad0b08760760487dab25a295d9abf3d3
Source dataset
uspto-grants-2015_01
Patent number
US08940736B2

Reaction notes

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