Trimethyl orthoformate → HCID 72948500, compound

HRID 921640Notes

Reaction equation

HRID 921640 reaction equation
[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]2)=[CH:6][C:5]([C:15]#[N:16])=[CH:4][C:3]=1[NH:17][C:18]1[N:23]=[C:22]([N:24]([CH:34]2[CH2:36][CH2:35]2)CC2C=CC(OC)=CC=2)[C:21]2=[N:37][CH:38]=[C:39]([C:40]#[N:41])[N:20]2[N:19]=1.[F:42][C:43]1([F:48])[CH2:46][CH:45]([NH2:47])[CH2:44]1.C(OC)(OC)OC.C([BH3-])#N.[Na+]>CO.O1CCCC1.O>[Cl:1][C:2]1[C:7]([N:8]2[CH2:9][CH2:10][CH:11]([NH:47][CH:45]3[CH2:46][C:43]([F:48])([F:42])[CH2:44]3)[CH2:12][CH2:13]2)=[CH:6][C:5]([C:15]#[N:16])=[CH:4][C:3]=1[NH:17][C:18]1[N:23]=[C:22]([NH:24][CH:34]2[CH2:35][CH2:36]2)[C:21]2=[N:37][CH:38]=[C:39]([C:40]#[N:41])[N:20]2[N:19]=1

Participants

8

Reactant 4

HCID 9005Trimethyl orthoformateHCID 5003444Sodium cyanoborohydrideHCID 225009513,3-Difluorocyclobutan-1-amineHCID 86708485HCID 86708485, compound2×

Product 1

HCID 72948500HCID 72948500, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a vial charged with 2-((2-chloro-5-cyano-3-(4-oxopiperidin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Intermediate 13) (30 mg, 0.053 mmol) and 3,3-difluorocyclobutanamine (6.79 mg, 0.063 mmol) in methanol (132 μl) and tetrahydrofuran (132 μl) was added trimethyl orthoformate (58.4 μl, 0.528 mmol). The reaction mixture was stirred at room temperature. Sodium cyanoborohydride (6.64 mg, 0.106 mmol) was added and the reaction mixture was stirred at room temperature 6 h. The reaction mixture was diluted with water and methanol and filtered. The solid was taken up in DMF and partitioned between water and ethyl acetate. The aqueous layer was washed with ethyl acetate (3×). The combined organics were washed with 10% lithium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude material was taken forward as is.

Workup

  1. stirringthe reaction mixture was stirred at room temperature 6 h
  2. filtrationfiltered
  3. custompartitioned between water and ethyl acetate
  4. washThe aqueous layer was washed with ethyl acetate (3×)
  5. washThe combined organics were washed with 10% lithium chloride solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6be7fbc5d481466fa23d04a7b70160d5
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

Loading…