Morpholine → HCID 89922660, compound

HRID 921926Notes

Reaction equation

HRID 921926 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][C:10](=O)[CH3:11])[C:5]([C:13]#[N:14])=[CH:4][C:3]=1[NH:15][C:16]1[N:21]=[C:20]([N:22]([CH:32]2[CH2:34][CH2:33]2)CC2C=CC(OC)=CC=2)[C:19]2=[N:35][CH:36]=[C:37]([C:38]#[N:39])[N:18]2[N:17]=1.[NH:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1.C(OC)(OC)OC.C([BH3-])#N.[Na+]>C1COCC1.CO.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][CH:10]([N:40]2[CH2:45][CH2:44][O:43][CH2:42][CH2:41]2)[CH3:11])[C:5]([C:13]#[N:14])=[CH:4][C:3]=1[NH:15][C:16]1[N:21]=[C:20]([NH:22][CH:32]2[CH2:34][CH2:33]2)[C:19]2=[N:35][CH:36]=[C:37]([C:38]#[N:39])[N:18]2[N:17]=1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 9005Trimethyl orthoformateHCID 5003444Sodium cyanoborohydrideHCID 89922506HCID 89922506, compound

Product 1

HCID 89922660HCID 89922660, compoundYield 42.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-((2-chloro-5-cyano-4-(3-oxobutyl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (38 mg, 0.070 mmol) and morpholine (9.2 mg, 0.10 mmol) was taken up in THF (0.2 mL) and MeOH (0.2 mL). Trimethyl orthoformate (0.078 mL, 0.070 mmol) and sodium cyanoborohydride (8.8 mg, 0.14 mmol) was then added. The reaction was stirred at room temperature overnight. The reaction was diluted with EtOAc and washed with aq. NaHCO3, then brine. The organic layer was dried over Na2SO4, filtered, and concentrated. The material was taken up in DCM (0.25 mL) and anisole (0.025 mL) was added, followed by TFA (0.25 mL). The reaction was stirred at room temperature overnight. The reaction was then concentrated in vacuo and purified by preparative HPLC to provide 2-((2-chloro-5-cyano-4-(3-morpholinobutyl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (15.3 mg, 0.030 mmol, 42.5% yield).

Workup

  1. washwashed with aq. NaHCO3
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additionanisole (0.025 mL) was added
  6. stirringThe reaction was stirred at room temperature overnight
  7. concentrationThe reaction was then concentrated in vacuo
  8. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-d85d5508643049b4b9fb2602f9b8b9ed
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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