Acetic Acid → HCID 86708603, compound

HRID 921722Notes

Reaction equation

HRID 921722 reaction equation
[NH2:1][CH: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][CH2:3]1.C(OC)(OC)OC.CC(O)=O.[O:43]1[CH2:46][C:45](=O)[CH2:44]1.C([BH3-])#N.[Na+]>C1COCC1.CO>[Cl:31][C:9]1[C:8]([N:5]2[CH2:6][CH2:7][CH:2]([NH:1][CH:45]3[CH2:46][O:43][CH2:44]3)[CH2:3][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

8

Reactant 5

HCID 176Acetic AcidHCID 9005Trimethyl orthoformateHCID 5003444Sodium cyanoborohydrideHCID 150242543-OxetanoneHCID 86708581HCID 86708581, compound

Product 1

HCID 86708603HCID 86708603, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-((3-(4-aminopiperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 329) (48 mg, 0.110 mmol) was taken up in THF (2 mL) and Methanol (2 mL) and trimethyl orthoformate (0.5 mL, 4.52 mmol), AcOH (0.05 mL, 0.873 mmol) in a round bottom flask. Oxetan-3-one (0.1 mL, 1.560 mmol) was added. The reaction mixture was stirred at room temperature for 15 mins. Sodium cyanoborohydride (50 mg, 0.796 mmol) was added and the reaction was stirred at room temperature for 2 hrs. LC/MS showed about 40% conversion to the desired product. Another batch of oxetan-3-one (0.1 mL, 1.560 mmol), trimethyl orthoformate (0.5 mL, 4.52 mmol), AcOH (0.05 mL, 0.873 mmol) and sodium cyanoborohydride (50 mg, 0.796 mmol) were added to the reaction mixture and let stirred for another 30 mins. LC/MS showed completed conversion to the product. The mixture was concentrated to almost dryness, diluted with EtOAc and washed with NaHCO3, then brine, dried over MgSO4 and concentrated. The crude was then purified by PREP-HPLC to give 21.3 mg of desired product

Workup

  1. stirringthe reaction was stirred at room temperature for 2 hrs

Sources & evidence

ORD record
ord-14e723a198fd4bbbb8bff88518380540
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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