Triethylamine → HCID 86717546, compound

HRID 712091Notes

Reaction equation

HRID 712091 reaction equation
[OH:1][C@@H:2]([C:4]1[N:15]([C@H:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:22](=[O:28])[CH2:23][CH2:24][C:25]([OH:27])=O)[CH2:17]2)[C:7]2=[C:8]3[S:14][CH:13]=[CH:12][C:9]3=[N:10][CH:11]=[C:6]2[N:5]=1)[CH3:3].C(=O)([O-])[O-].[NH4+].[NH4+].C([N:37](CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O.C(OCC)(=O)C.CO.ClCCl>[OH:1][C@@H:2]([C:4]1[N:15]([C@H:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:22](=[O:28])[CH2:23][CH2:24][C:25]([NH2:37])=[O:27])[CH2:17]2)[C:7]2=[C:8]3[S:14][CH:13]=[CH:12][C:9]3=[N:10][CH:11]=[C:6]2[N:5]=1)[CH3:3]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 517111Ammonium CarbonateHCID 86717545HCID 86717545, compound

Product 1

HCID 86717546HCID 86717546, compoundYield 17.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

To a mixture of 4-((3S)-3-{2-[(1R)-1-hydroxyethyl]-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-1-yl}piperidin-1-yl)-4-oxobutanoic acid (35 mg, 0.087 mmol), ammonium carbonate (42 mg, 0.43 mmol), and triethylamine (18.2 μL, 0.130 mmol) in N,N-dimethylformamide (0.6 mL) was added benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (76.9 mg, 0.174 mmol). The resulting mixture was stirred at room temperature for 2.5 h. The mixture was diluted with ethyl acetate then washed with sat. NaHCO3, water, and brine. LCMS showed most of the desired product remained in the aqueous layer. The aqueous layer was concentrated to give white solids. The solids were stirred in ˜1:1 MeOH/dichloromethane and then filtered to give 40 mg crude product. The crude was purified using RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give 6 mg of the desired product. LCMS calculated for C19H24N5O3S (M+H)+: m/z=402.2. Found: 402.0.

Workup

  1. washthen washed with sat. NaHCO3, water, and brine
  2. concentrationThe aqueous layer was concentrated
  3. customto give white solids
  4. filtrationfiltered
  5. customto give 40 mg crude product
  6. customThe crude was purified
  7. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-90ac6a5332f5480f8eff2de6d7785eda
Source dataset
uspto-grants-2015_11
Patent number
US09181271B2

Reaction notes

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