Dimethylacetamide → HCID 86677717, compound

HRID 1499790Notes

Reaction equation

HRID 1499790 reaction equation
Cl[C:2]1[C:3]([CH3:32])=[C:4]([CH:25]2[CH2:28][N:27]([CH:29]([CH3:31])[CH3:30])[CH2:26]2)[C:5]([O:23][CH3:24])=[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]([CH:20]([F:22])[F:21])=[N:11]2)[CH3:9])[CH:7]=1.[CH3:33][N:34](C)C(=O)C>NC1N=CN=C2N(C(C3C(OC)=C(C4C=CN=C(C(N(CCO)C)=O)C=4)C(C)=C(C#N)C=3)C)N=C(C)C=12.[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:23][CH3:24])=[C:4]([CH:25]4[CH2:26][N:27]([CH:29]([CH3:31])[CH3:30])[CH2:28]4)[C:3]([CH3:32])=[C:2]([CH:7]=3)[C:33]#[N:34])[CH3:9])[N:11]=[C:12]([CH:20]([F:21])[F:22])[C:13]=12

Participants

6

Reactant 2

HCID 31374DimethylacetamideHCID 71509658HCID 71509658, compound

Product 1

HCID 86677717HCID 86677717, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 71510901HCID 71510901, compoundCatalyst

Conditions

Temperature
120 °C

Procedure

0.5 mL of the preformed catalyst (from Example 40) was added to a mixture of 1-{1-[5-chloro-3-(1-isopropylazetidin-3-yl)-2-methoxy-4-methylphenyl]ethyl}-3-(difluoromethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (22 mg, 0.047 mmol), zinc (1.3 mg, 0.021 mmol) and zinc cyanide (5.6 mg, 0.047 mmol) in N,N-dimethylacetamide (0.7 mL). The mixture was flushed with N2 and heated at 120° C. overnight. The reaction was about 50% complete and was stopped there so that both compounds could be isolated. The reaction mixture was filtered, washing with dichloromethane, and concentrated. 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 both title compounds. The products were isolated as a racemic mixture. Example 126: Yield=6.6 mg (30%); LCMS calculated for C22H28ClF2N6O (M+H)+: m/z=465.2; Found: 465.2; Example 127: Yield=3.0 mg (14%); LCMS calculated for C23H28F2N7O (M+H)+: m/z=456.2; Found: 456.2.

Workup

  1. customThe mixture was flushed with N2
  2. customcould be isolated
  3. filtrationThe reaction mixture was filtered
  4. washwashing with dichloromethane
  5. concentrationconcentrated
  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)
  8. customto give both title compounds
  9. customThe products were isolated as a racemic mixture

Sources & evidence

ORD record
ord-1db38a4762c94390a003a0237e177cc0
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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