Water → 1-(1-Methyl-6-(2-oxa-6-azaspiro[3,3]heptan-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine

HRID 75313Notes

Reaction equation

HRID 75313 reaction equation
[CH3:1][Mg]Br.[CH3:4][N:5]1[C:13]2[C:8](=[N:9][C:10]([C:21]#[N:22])=[C:11]([N:14]3[CH2:20][C:16]4([CH2:19][O:18][CH2:17]4)[CH2:15]3)[CH:12]=2)[CH:7]=[CH:6]1.[BH4-].[Na+].O>C1COCC1>[CH3:4][N:5]1[C:13]2[C:8](=[N:9][C:10]([CH:21]([NH2:22])[CH3:1])=[C:11]([N:14]3[CH2:20][C:16]4([CH2:19][O:18][CH2:17]4)[CH2:15]3)[CH:12]=2)[CH:7]=[CH:6]1

Participants

6

Reactant 4

HCID 962WaterHCID 4311764Sodium borohydrideHCID 867080111-Methyl-6-(2-oxa-6-azaspiro[3,3]heptan-6-yl)-1H-pyrrolo[3,2-b]pyridine-5-carbonitrileHCID 178418573HCID 178418573, compound

Product 1

HCID 867080131-(1-Methyl-6-(2-oxa-6-azaspiro[3,3]heptan-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamineYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

Methylmagnesium bromide (1.56 mL, 2.18 mmol) was added slowly to a stirred solution of 1-methyl-6-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1H-pyrrolo[3,2-b]pyridine-5-carbonitrile (222 mg, 0.873 mmol) in THF (20 mL). The reaction was stirred at 40° C. for 1.5 hours, then cooled to 0° C. and quenched with MeOH (10 mL). After 10 minutes, sodium tetrahydroborate (83 mg, 2.18 mmol) was added. The reaction mixture was stirred for 20 minutes. Water (1 mL) was added and the reaction mixture was stirred for an additional 10 minutes. The reaction mixture was dried over MgSO4, filtered through Celite, and concentrated. The crude product was purified by basic silica column chromatography (3-5% MeOH in DCM) to give the title compound as a clear oil (111 mg, 47%). 1H NMR (500 MHz, CD3OD) δ ppm 7.28 (d, 1H, J=3.5 Hz), 7.14 (s, 1H), 6.47 (d, 1H, J=3.5 Hz), 4.89 (s, 4H), 4.33 (q, 1H, J=7.0 Hz), 4.10 (qAB, 4H, J=35.5, 7.5 Hz), 3.36 (s, 3H), 1.43 (d, 3H, J=7.0 Hz). ESI-MS m/z [M+H]+ calc'd for C15H20F4O, 273; found 273.

Workup

  1. temperaturecooled to 0° C.
  2. customquenched with MeOH (10 mL)
  3. waitAfter 10 minutes
  4. stirringThe reaction mixture was stirred for 20 minutes
  5. stirringthe reaction mixture was stirred for an additional 10 minutes
  6. dry with materialThe reaction mixture was dried over MgSO4
  7. filtrationfiltered through Celite
  8. concentrationconcentrated
  9. customThe crude product was purified by basic silica column chromatography (3-5% MeOH in DCM)

Sources & evidence

ORD record
ord-0505a6024c8a4371bc66a028d1f0ab44
Source dataset
uspto-grants-2014_09
Patent number
US08835420B2

Reaction notes

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