Tetrahydrofuran → HCID 66600042, compound

HRID 1622003Notes

Reaction equation

HRID 1622003 reaction equation
[CH3:1][O:2][C:3]1[CH:44]=[CH:43][C:6]([CH2:7][N:8]([CH2:34][C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[C:17]([NH:24][C:25]4[CH:26]=[N:27][C:28]([O:32][CH3:33])=[C:29]([F:31])[CH:30]=4)=[N:18][CH:19]=[C:20]([CH:23]=3)[CH:21]=O)[N:10]=2)=[CH:5][CH:4]=1.[CH3:45][C@@H:46]1[CH2:51][NH:50][CH2:49][CH2:48][N:47]1[C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53].O1CCCC1.C([BH3-])#N.[Na+]>[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[CH3:42][O:41][C:38]1[CH:37]=[CH:36][C:35]([CH2:34][N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:44][CH:43]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:23]=[C:20]([CH2:21][N:50]4[CH2:49][CH2:48][N:47]([C:52]([O:54][C:55]([CH3:57])([CH3:56])[CH3:58])=[O:53])[C@H:46]([CH3:45])[CH2:51]4)[CH:19]=[N:18][C:17]=3[NH:24][C:25]3[CH:26]=[N:27][C:28]([O:32][CH3:33])=[C:29]([F:31])[CH:30]=3)[N:10]=2)=[CH:40][CH:39]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 5003444Sodium cyanoborohydrideHCID 10262201tert-Butyl (2R)-2-methylpiperazine-1-carboxylateHCID 715003625-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)nicotinaldehyde

Product 1

HCID 66600042HCID 66600042, compoundYield 74.1%

Reagents, catalysts & solvents 1

HCID 76524Titanium tetraethoxideCatalyst

Conditions

Temperature
70 °C

Procedure

To a 15 mL round-bottomed flask was added 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)nicotinaldehyde (0.438 g, 0.735 mmol), (R)-tert-butyl 2-methylpiperazine-1-carboxylate (0.368 g, 1.838 mmol), tetrahydrofuran (0.053 g, 0.735 mmol), titanium (iv) ethoxide (0.761 mL, 3.68 mmol) (Aldrich). The flask was sealed and the solution was stirred at 70° C. overnight. The solution was stirred at 0° C. and treated in one portion with sodium cyanotrihydridoborate (0.462 g, 7.35 mmol) (Aldrich). The suspension was stirred at 0° C. for two hours. The suspension was quenched with drops of MeOH and water, then DCM. The suspension was stirred for 10 minutes vigorously and was filtered through Celite® (diatomaceous earth) and the filtrated cake was washed with DCM. The organic phase was concentrated to afford (R)-tert-butyl 4-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)methyl)-2-methylpiperazine-1-carboxylate (0.425 g, 0.545 mmol, 74.1% yield).

Workup

  1. customThe flask was sealed
  2. stirringThe solution was stirred at 0° C.
  3. stirringThe suspension was stirred at 0° C. for two hours
  4. customThe suspension was quenched with drops of MeOH and water
  5. stirringThe suspension was stirred for 10 minutes vigorously
  6. filtrationwas filtered through Celite® (diatomaceous earth)
  7. washthe filtrated cake was washed with DCM
  8. concentrationThe organic phase was concentrated

Sources & evidence

ORD record
ord-ccba48da25bc4ff0b77f76eaf6075600
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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