Propionic Acid → HCID 71509092, compound

HRID 1499930Notes

Reaction equation

HRID 1499930 reaction equation
F[C:2](F)(F)[C:3]([OH:5])=O.F[C:9](F)(F)[C:10]([OH:12])=O.[NH2:15][C:16]1[N:21]=[CH:20][N:19]=[C:18]2[N:22]([CH:26]([C:28]3[CH:35]=[C:34]([CH3:36])[C:31]([C:32]#[N:33])=[C:30]([CH:37]4[CH2:40][NH:39][CH2:38]4)[C:29]=3OCC)[CH3:27])[N:23]=[C:24]([CH3:25])[C:17]=12.CCN(C(C)C)C(C)C.[C:53](O)(=[O:56])CC.F[P-](F)(F)(F)(F)F.[CH3:65][N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1>CN(C)C=O>[NH2:15][C:16]1[N:21]=[CH:20][N:19]=[C:18]2[N:22]([CH:26]([C:28]3[CH:35]=[C:34]([CH3:36])[C:31]([C:32]#[N:33])=[C:30]([CH:37]4[CH2:40][N:39]([C:53](=[O:56])[C:10]([OH:12])([CH3:9])[CH3:65])[CH2:38]4)[C:29]=3[O:5][CH2:3][CH3:2])[CH3:27])[N:23]=[C:24]([CH3:25])[C:17]=12

Participants

6

Reactant 4

HCID 1032Propionic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86677847HCID 86677847, compound2×

Product 1

HCID 71509092HCID 71509092, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The 4-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-2-azetidin-3-yl-3-ethoxy-6-methylbenzonitrile (0.075 g, 0.10 mmol, chiral intermediate from Example 320, Step 1) was dissolved in N,N-dimethylformamide (3.0 mL) and DIPEA (0.089 mL, 0.51 mmol) and the propanoic acid, 2-hydroxy-2-methyl-(0.013 g, 0.12 mmol) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (0.058 g, 0.15 mmol) were added. The reaction was stirred at room temperature for 18 hrs and was complete by LC/MS. The product was purified without workup by prep HPLC on a C-18 column eluting water:acetonitrile gradient buffered to pH 10 to give the title compound as a white amorphous solid (0.025 g, 51%). The product was isolated as a single enantiomer. LCMS calculated for C25H32N7O3(M+H)+: m/z=478.2; found: 478.2. 1H NMR (300 MHz, DMSO-d6) δ 8.10 (s, 1H), 7.29 (s, 1H), 6.24 (q, J=6.8 Hz, 1H), 5.07 (s, 1H), 4.90-4.75 (m, 1H), 4.73-4.58 (m, 1H), 4.39 (p, J=8.5 Hz, 1H), 4.30-4.05 (m, 2H), 3.75 (d, J=7.1 Hz, 2H), 2.54 (s, 3H), 2.38 (s, 3H), 1.72 (d, J=6.9 Hz, 3H), 1.35 (t, J=6.1 Hz, 3H), 1.26 (s, 3H), 1.23 (s, 3H).

Workup

  1. customThe product was purified without workup by prep HPLC on a C-18 column
  2. washeluting water

Sources & evidence

ORD record
ord-41e322884b84400692d236ff30bbf863
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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