Acetic Acid → HCID 89923144, compound

HRID 921836Notes

Reaction equation

HRID 921836 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][CH:10]=O)[C:5]([C:12]#[N:13])=[CH:4][C:3]=1[NH:14][C:15]1[N:20]=[C:19]([N:21]([CH:31]2[CH2:33][CH2:32]2)[CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:18]2=[N:34][CH:35]=[C:36]([C:37]#[N:38])[N:17]2[N:16]=1.[NH:39]1[CH2:44][CH2:43][CH:42]([C:45]([OH:48])([CH3:47])[CH3:46])[CH2:41][CH2:40]1.CC(O)=O.C([BH3-])#N.[Na+]>>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][CH2:10][N:39]2[CH2:44][CH2:43][CH:42]([C:45]([OH:48])([CH3:47])[CH3:46])[CH2:41][CH2:40]2)[C:5]([C:12]#[N:13])=[CH:4][C:3]=1[NH:14][C:15]1[N:20]=[C:19]([N:21]([CH:31]2[CH2:32][CH2:33]2)[CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:18]2=[N:34][CH:35]=[C:36]([C:37]#[N:38])[N:17]2[N:16]=1

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 52003212-(4-Piperidyl)-2-propanolHCID 89923126HCID 89923126, compound

Product 1

HCID 89923144HCID 89923144, compoundYield 70.7%

Procedure

2-((2-chloro-5-cyano-4-(3-oxopropyl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (49 mg, 0.093 mmol) was taken up in TIIF (1 mL) and 2-(piperidin-4-yl)propan-2-ol (26.6 mg, 0.186 mmol), AcOH (5.32 μl, 0.093 mmol), and sodium cyanoborohydride (11.69 mg, 0.186 mmol) were added. The reaction was stirred at room temperature overnight. The reaction mixture was quenched with 2M K3PO4 solution and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated. The material was purified by flash column chromatography (0-100% EtOAc/DCM then flushed with 10% MeOH/DCM; 24 g column). 2-((2-chloro-5-cyano-4-(3-(4-(2-hydroxypropan-2-yl)piperidin-1-yl)propyl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (43 mg) was obtained as a yellow glass.

Workup

  1. additionwere added
  2. customThe reaction mixture was quenched with 2M K3PO4 solution
  3. extractionextracted with EtOAc
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe material was purified by flash column chromatography (0-100% EtOAc/DCM
  8. customthen flushed with 10% MeOH/DCM

Sources & evidence

ORD record
ord-437f7978d1c34050b4c4d86eaac07ecd
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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