Nitromethane → HCID 86677851, compound

HRID 1499933Notes

Reaction equation

HRID 1499933 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[C:15]([O:28][CH2:29][CH3:30])=[C:16](/[CH:22]=[CH:23]/[C:24]([O:26][CH3:27])=[O:25])[C:17]([CH3:21])=[C:18]([Cl:20])[CH:19]=3)[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12.N12CCCN=C1CCCCC2.[N+:42]([CH3:45])([O-:44])=[O:43]>>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[C:15]([O:28][CH2:29][CH3:30])=[C:16]([CH:22]([CH2:45][N+:42]([O-:44])=[O:43])[CH2:23][C:24]([O:26][CH3:27])=[O:25])[C:17]([CH3:21])=[C:18]([Cl:20])[CH:19]=3)[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12

Participants

4

Reactant 3

HCID 6375NitromethaneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86677849HCID 86677849, compound

Product 1

HCID 86677851HCID 86677851, compoundYield 48%

Conditions

Temperature
90 °C

Procedure

A solution of methyl (2E)-3-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-ethoxy-6-methylphenyl}acrylate (0.40 g, 0.93 mmol) in nitromethane (6.3 mL) was treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (0.14 mL, 0.93 mmol) and stirred at 90° C. for 22 h. The reaction mixture was concentrated, diluted with methanol, and purified by preparative LCMS (XBridge C18 Column, eluting with a gradient of acetonitrile in water with 0.1% trifluoroacetic acid, at flow rate of 60 mL/min). The LCMS fractions were concentrated to remove acetonitrile, treated with solid sodium bicarbonate, and extracted into ethyl acetate. The ethyl acetate was concentrated to give the desired product (0.22 g, 48%) as a mixture of diastereoisomers. LCMS for C22H28ClN6O5 (M+H)+: m/z=491.2; Found: 491.2.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with methanol
  3. custompurified by preparative LCMS (XBridge C18 Column
  4. washeluting with a gradient of acetonitrile in water with 0.1% trifluoroacetic acid, at flow rate of 60 mL/min)
  5. concentrationThe LCMS fractions were concentrated
  6. customto remove acetonitrile
  7. additiontreated with solid sodium bicarbonate
  8. extractionextracted into ethyl acetate
  9. concentrationThe ethyl acetate was concentrated

Sources & evidence

ORD record
ord-a5c74ec3c7c34ef08aa5ef4611a0552b
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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