Formaldehyde → HCID 69564455, compound

HRID 1072459Notes

Reaction equation

HRID 1072459 reaction equation
[C:1](O)(=O)/C=C/C(O)=O.[F:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][CH:14]=[C:13]2[C@H:19]1[CH2:23][CH2:22][C@@H:21]([NH:24][CH2:25][C@@H:26]2[O:40][C:30]3=[C:31]4[C:36](=[CH:37][CH:38]=[C:29]3[O:28][CH2:27]2)[N:35]=[C:34]([CH3:39])[CH:33]=[CH:32]4)[CH2:20]1.C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1.CO>[F:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][CH:14]=[C:13]2[C@H:19]1[CH2:23][CH2:22][C@@H:21]([N:24]([CH3:1])[CH2:25][C@@H:26]2[O:40][C:30]3=[C:31]4[C:36](=[CH:37][CH:38]=[C:29]3[O:28][CH2:27]2)[N:35]=[C:34]([CH3:39])[CH:33]=[CH:32]4)[CH2:20]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 69565198HCID 69565198, compound

Product 1

HCID 69564455HCID 69564455, compoundYield 70.7%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a mixture of N-[(1R*,3S*)-3-(5-fluoro-1H-indol-3-yl)cyclopentyl]-N-{[(2S)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl}amine fumarate (200 mg, 0.365 mmol) and formaldehyde (37%, 50 μL, 0.67 mmol) in 2:1 tetrahydrofuran/methanol (3 mL) was added sodium triacetoxyborohydride (155 mg, 0.73 mmol). The reaction was allowed to stir at ambient temperature overnight, then was quenched with saturated aqueous sodium bicarbonate (20 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (2×20 cm silica gel, 3% methanol/methylene chloride) afforded 115 mg (70%) of the title compound as a semi-solid, which was converted to its fumarate salt as a white powder: mp 198-199° C. (dec); MS (ES) m/z 446 [M+H]+.[α]D5.3°(c 1.0, DMSO)

Workup

  1. customwas quenched with saturated aqueous sodium bicarbonate (20 mL)
  2. extractionextracted with ethyl acetate (3×20 mL)
  3. washThe combined organic layers were washed with brine (30 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6f1d5ff07ec04c1d81b07256d8e9bcc9
Source dataset
uspto-grants-2005_06
Patent number
US06911445B2

Reaction notes

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