4-Methoxybenzylamine → N-benzyl-1-(6-chloro-3-iodo-1-trityl-1H-pyrazolo[4,3-c]pyridin-4-yl)propan-2-amine

HRID 590841Notes

Reaction equation

HRID 590841 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]2[C:9]([I:31])=[N:10][N:11]([C:12]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:4]=2[CH:3]=1.CO[C:34](OC)([N:36]([CH3:38])C)[CH3:35].CO[C:43]1[CH:50]=[CH:49][C:46](CN)=[CH:45][CH:44]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CCO.CC(O)=O.ClCCCl>[CH2:38]([NH:36][CH:34]([CH3:35])[CH2:8][C:6]1[C:5]2[C:9]([I:31])=[N:10][N:11]([C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:4]=2[CH:3]=[C:2]([Cl:1])[N:7]=1)[C:43]1[CH:50]=[CH:49][CH:46]=[CH:45][CH:44]=1

Participants

8

Reactant 4

HCID 754524-MethoxybenzylamineHCID 878351,1-Dimethoxyethyl(dimethyl)amineHCID 5049666Sodium triacetoxyborohydrideHCID 1181689626-chloro-3-iodo-4-methyl-1-trityl-1H-pyrazolo[4,3-c]pyridine2×

Product 1

HCID 118272365N-benzyl-1-(6-chloro-3-iodo-1-trityl-1H-pyrazolo[4,3-c]pyridin-4-yl)propan-2-amine

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolvent2×HCID 702EthanolSolvent

Procedure

6-chloro-3-iodo-trityl-1H-pyrazolo[4.3-c]pyridine (Intermediate 1C, 2 g, 3.73 mmol), N, N dimethylacetamide-dimethyl acetal (DMA-DMA) (4.97 g, 37.3 mmol) were stirred at 125° C. for 12 hrs. Reaction was concentrated and excess DMF-DMA azeotroped with Toluene. The resulting intermediate and p-methoxybenzylamine (2.05 g, 14.9 mmol) were stirred in a 3:1:1 solution of DCE:AcOH:EtOH (20 ml) at 85° C. for 3 hrs. Solvent was removed by vacuum and the residue was taken in DCE (15 ml) followed with addition of sodium triacetoxyborohydride (3.16 g, 14.9 mmol) and acetic acid (0.9 g, 14.9 mmol) before the mixture was stirred at room temperature for 6 hours. The reaction mixture was partitioned between DCM and aqueous sodium bicarbonate and the organics was separated, washed with brine, dried with sodium sulfate and concentrated. Purification of the residue by flash column (0-90% -EtOAc-hexanes) gave N-benzyl-1-(6-chloro-3-iodo-1-trityl-1H-pyrazolo[4,3-c]pyridin-4-yl)propan-2-amine MS ESI calc'd. for C35H30ClIN4 [M+H]+ 700. found 700.

Workup

  1. customReaction
  2. concentrationwas concentrated
  3. customexcess DMF-DMA azeotroped with Toluene
  4. customSolvent was removed by vacuum
  5. customThe reaction mixture was partitioned between DCM and aqueous sodium bicarbonate
  6. customthe organics was separated
  7. washwashed with brine
  8. dry with materialdried with sodium sulfate
  9. concentrationconcentrated
  10. customPurification of the residue by flash column (0-90% -EtOAc-hexanes)

Sources & evidence

ORD record
ord-6f65678903ce46e99ca606cc88ed4335
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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