Dimethylacetamide → HCID 86677780, compound

HRID 1499857Notes

Reaction equation

Cl[C:2]1[C:3]([CH3:29])=[C:4]([C:23]2[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=2)[C:5]([O:21][CH3:22])=[C:6]([CH:8]([N:10]2[C:14]3=[N:15][CH:16]=[N:17][C:18]([NH2:19])=[C:13]3[C:12]([CH3:20])=[N:11]2)[CH3:9])[CH:7]=1.[CH3:30][N:31](C)C(=O)C>[Zn].[C-]#N.[Zn+2].[C-]#N>[NH2:19][C:18]1[N:17]=[CH:16][N:15]=[C:14]2[N:10]([CH:8]([C:6]3[C:5]([O:21][CH3:22])=[C:4]([C:23]4[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=4)[C:3]([CH3:29])=[C:2]([CH:7]=3)[C:30]#[N:31])[CH3:9])[N:11]=[C:12]([CH3:20])[C:13]=12

Participants

Conditions

Temperature: 120 °C

Procedure

Pre-formed catalyst (0.05 mL, from Example 40) was added to a mixture 1-{1-[5-chloro-2-methoxy-4-methyl-3-(1-methyl-1H-pyrazol-4-yl)phenyl]ethyl}-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (7.7 mg, 0.019 mmol), zinc (0.54 mg, 0.0082 mmol) and zinc cyanide (2.2 mg, 0.019 mmol) in N,N-dimethylacetamide (0.3 mL). The mixture was degassed with nitrogen 3 times. The reaction was heated at 120° C. for 1.5 h. 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 the desired product (2.1 mg, 27%). The product was isolated as a single enantiomer. LCMS calculated for C21H23N8O (M+H)+: m/z=403.2; Found: 403.2.

Workup

customPre-formed catalyst (0.05 mL, from Example 40)
customThe mixture was degassed with nitrogen 3 times
customThe crude was purified
washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)

Sources & evidence

ORD record: ord-9673d3c104954a3a9322e0f62505450d
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199982B2

Reaction notes

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