4-Methylmorpholine → HCID 178463565, compound

HRID 243460Notes

Reaction equation

HRID 243460 reaction equation
[NH:1]1[CH2:4][CH:3]([N:5]2[C:9]3[CH:10]=[C:11]([F:14])[CH:12]=[CH:13][C:8]=3[N:7]=[C:6]2[C@@H:15]([NH:17][C:18]2[N:26]=[CH:25][N:24]=[C:23]3[C:19]=2[N:20]=[CH:21][NH:22]3)[CH3:16])[CH2:2]1.[CH3:27][N:28]1[CH2:33]C[O:31][CH2:30][CH2:29]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:27][N:28]([CH3:33])[CH2:29][C:30]([N:1]1[CH2:2][CH:3]([N:5]2[C:9]3[CH:10]=[C:11]([F:14])[CH:12]=[CH:13][C:8]=3[N:7]=[C:6]2[CH:15]([NH:17][C:18]2[N:26]=[CH:25][N:24]=[C:23]3[C:19]=2[N:20]=[CH:21][NH:22]3)[CH3:16])[CH2:4]1)=[O:31]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178461940HCID 178461940, compound

Product 1

HCID 178463565HCID 178463565, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of [(S)-1-(1-azetidin-3-yl-6-fluoro-1H-benzoimidazol-2-yl)ethyl]-(9H-purin-6-yl)amine (75 mg, 0.21 mmol) dimethylaminoacetic acid (25 mg. 0.23 mmol), 4-methylmorpholine (70 μL, 0.64 mmol) and HATU (93 mg, 0.24 mmol) in DMF (2 mL) was stirred at RT for 4 h. The crude mixture was partitioned between EtOAc and a saturated aqueous solution of NaHCO3. The aqueous phase was further extracted with EtOAc and the combined organic fractions washed with water, followed by brine, dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2N NH3/MeOH in DCM) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a gradient 5-60%, 0.1% NH4OH in acetonitrile/water) to afford 381 as a white solid (20 mg, 22%). LCMS (Method K): RT 1.86 min [M+H]+ 438.1. 1H NMR (DMSO-d6, 400 MHz): δ 8.30-7.92 (3H, m), 7.71-7.63 (1H, m), 7.45-7.34 (1H, m), 7.11 (1H, t, J=9.36 Hz), 5.93-5.58 (2H, m), 4.82-4.69 (1H, m), 4.67-4.56 (1H, m), 4.49-4.34 (1H, m), 4.25-4.26 (1H, m), 3.14 (1H, d, J=14.18 Hz), 2.89 (1H, dd, J=14.18, 3.84 Hz), 2.23 (3H, s), 2.22 (3H, s), 1.67 (3H, d, J=6.66 Hz)

Workup

  1. customThe crude mixture was partitioned between EtOAc
  2. extractionThe aqueous phase was further extracted with EtOAc
  3. washthe combined organic fractions washed with water
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2N NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-c8c2c77b79334cb996f6cfe3144577bd
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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