Triethylamine → HCID 56967198, compound

HRID 1428262Notes

Reaction equation

HRID 1428262 reaction equation
[NH:1]1[CH:9]2[CH:4]([N:5]([C:10]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:11])[CH2:6][CH2:7][CH2:8]2)[CH2:3][CH2:2]1.CCN(CC)CC.Cl[C:28]1[CH:33]=[CH:32][N:31]=[C:30]2[NH:34][CH:35]=[CH:36][C:29]=12>CN1C(=O)CCC1>[NH:34]1[C:30]2=[N:31][CH:32]=[CH:33][C:28]([N:1]3[CH:9]4[CH:4]([N:5]([C:10]([O:12][CH2:13][C:14]5[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=5)=[O:11])[CH2:6][CH2:7][CH2:8]4)[CH2:3][CH2:2]3)=[C:29]2[CH:36]=[CH:35]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 113894934-Chloro-1H-pyrrolo[2,3-b]pyridine2×HCID 68052018Benzyl octahydro-4H-pyrrolo[3,2-b]pyridine-4-carboxylate

Product 1

HCID 56967198HCID 56967198, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
160 °C

Procedure

To a stirred solution of the product of Example 1, Step 1 (136 mg, 0.524 mmol) in NMP (0.262 mL), in a microwave vial, was added Et3N (0.073 mL, 0.52 mmol) and 4-chloro-1H-pyrrolo[2,3-b]pyridine (16 mg, 0.11 mmol). The resulting solution was heated at 160° C. for 2 hours in a Biotage Initiator microwave. An additional 4 equivalents of 4-chloro-1H-pyrrolo[2,3-b]pyridine (64 mg, 0.42 mmol) was added to the reaction mixture and the resulting solution was stirred at 160° C. for another 2 hours in a Biotage Initiator microwave. The reaction mixture was cooled to ambient temperature and partitioned between EtOAc (50 mL) and saturated sodium bicarbonate (50 mL). The layers were separated, and the organic layer was collected, dried over sodium sulfate and concentrated in vacuo to afford a crude oil that was purified by reverse phase HPLC. Lyophilization of the product fractions afforded the title compound (TFA salt) as a white solid. LRMS calc'd for C22H25N4O2 [M+H]+, 377; found 377. Jak1 activity: +.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. custompartitioned between EtOAc (50 mL) and saturated sodium bicarbonate (50 mL)
  3. customThe layers were separated
  4. customthe organic layer was collected
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customto afford a crude oil that
  8. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-d78291508c4c4ab89365de40c40e2124
Source dataset
uspto-grants-2015_01
Patent number
US08937077B2

Reaction notes

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