Acetic Acid → HCID 86708674, compound

HRID 921781Notes

Reaction equation

HRID 921781 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]([CH3:30])[C:5]1[C:10]([C:11]#[N:12])=[CH:9][C:8]([NH:13][C:14]2[N:19]=[C:18]([NH:20][CH:21]3[CH2:23][CH2:22]3)[C:17]3=[N:24][CH:25]=[C:26]([C:27]#[N:28])[N:16]3[N:15]=2)=[C:7]([Cl:29])[CH:6]=1.[O:31]1[CH2:34][C:33](=O)[CH2:32]1.COC(OC)OC.C(O)(=O)C.C([BH3-])#N.[Na+]>CO.C(Cl)Cl>[Cl:29][C:7]1[CH:6]=[C:5]([N:4]([CH3:30])[CH2:3][CH2:2][NH:1][CH:33]2[CH2:34][O:31][CH2:32]2)[C:10]([C:11]#[N:12])=[CH:9][C:8]=1[NH:13][C:14]1[N:19]=[C:18]([NH:20][CH:21]2[CH2:22][CH2:23]2)[C:17]2=[N:24][CH:25]=[C:26]([C:27]#[N:28])[N:16]2[N:15]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 9005Trimethyl orthoformateHCID 5003444Sodium cyanoborohydrideHCID 150242543-OxetanoneHCID 86708675HCID 86708675, compound

Product 1

HCID 86708674HCID 86708674, compoundYield 14%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 2-((4-((2-aminoethyl)(methyl)amino)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 412)(63 mg, 0.149 mmol), oxetan-3-one (215 mg, 2.98 mmol), trimethylorthoformate (0.823 mL, 7.45 mmol), and acetic acid (0.085 mL, 1.490 mmol) in a mixture of MeOH (0.5 mL) and DCM (0.5 mL) was stirred at room temperature for 15 min. Added sodium cyanoborohydride (1M in THF, 1.49 mL, 1.49 mmol) and left the reaction stirring for 3 hrs. The reaction was partitioned between EtOAc and sat. aq. NaHCO3 solution. After stirring for 15 min, the aqueous phase was separated and washed with EtOAc. The combined organic phases were washed with brine, dried with sodium sulfate, and the solvent removed. Preparative HPLC (Column: Waters XBridge C18, 19×200 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: 20-60% B over 20 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min) afforded the title compound (10 mg).

Workup

  1. stirringstirring for 3 hrs
  2. customThe reaction was partitioned between EtOAc and sat. aq. NaHCO3 solution
  3. stirringAfter stirring for 15 min
  4. customthe aqueous phase was separated
  5. washwashed with EtOAc
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried with sodium sulfate
  8. customthe solvent removed
  9. waitGradient: 20-60% B over 20 minutes
  10. customa 5-minute hold

Sources & evidence

ORD record
ord-456f4c7928704675b1e74486201c8edc
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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