Pyrrolidine → HCID 57723820, compound

HRID 1987503Notes

Reaction equation

HRID 1987503 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[N:9]([CH2:20][C:21]3[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=3[C:23]#[N:24])[C:10](=[O:19])[C:11]3[CH:17]=[C:16](Cl)[N:15]=[CH:14][C:12]=3[N:13]=2)[CH2:3]1.[NH:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1.C(=O)(O)[O-].[Na+]>CCO.CCOC(C)=O>[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[N:9]([CH2:20][C:21]3[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=3[C:23]#[N:24])[C:10](=[O:19])[C:11]3[CH:17]=[C:16]([N:29]4[CH2:33][CH2:32][CH2:31][CH2:30]4)[N:15]=[CH:14][C:12]=3[N:13]=2)[CH2:3]1

Participants

6

Reactant 3

HCID 31268PyrrolidineHCID 516892Sodium BicarbonateHCID 57723817HCID 57723817, compound

Product 1

HCID 57723820HCID 57723820, compoundYield 41.9%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-[2-(3-(R)-Amino-piperidin-1yl)-6-chloro-4-oxo-4H-pyrido[3,4-d]pyrimidin-3-ylmethyl]-benzonitrile (Example 18) (120 mg, 0.3 mmol), pyrrolidine (75 μL, 0.91 mmol) and sodium bicarbonate (76 mg, 0.91 mmol) were stirred in EtOH in a sealed tube at 150° C. for 16 h. After cooling, the reaction was diluted with EtOAc, washed with brine, dried (MgSO4), and concentrated in vacuo. Purification by preparative HPLC yielded 54 mg (32%) of the title compound as a bright orange solid. 1H NMR (400 MHz, MeOD-d4): δ 8.40 (s, 1H), 7.64 (dd, 1H, J=7.6, 1.2 Hz), 7.48 (dt, 1H, J=7.6, 1.2 Hz), 7.33 (t, 1H, J=7.6 Hz), 7.07 (d, 1H, J=7.6 Hz), 6.67 (s, 1H), 5.43 (s, 2H), 3.20-3.32 (m, 5H), 3.02-3.10 (m, 1H), 2.81-2.90 (m, 1H), 2.69-2.78 (m, 1H), 2.59-2.67 (m, 1H), 1.87-1.99 (m, 5H), 1.51-1.73 (m, 2H), 1.18-1.28 (m, 1H). MS (ES) [m+H] calc'd for C24H27N7O 430; found 430.

Workup

  1. temperatureAfter cooling
  2. washwashed with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-31cd0354641642258c70e900af9d399d
Source dataset
uspto-grants-2009_06
Patent number
US07550590B2

Reaction notes

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