Dimethylacetamide → HCID 68358872, compound

HRID 1408953Notes

Reaction equation

HRID 1408953 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@@H:11]3[CH2:15][CH2:14][C@:13]([OH:17])([CH3:16])[C:12]3([CH3:19])[CH3:18])=[C:8]([C:20]([NH2:22])=[O:21])[CH:7]=[N:6][N:5]2[CH:23]=1.C1(C2C3C(=CC=CC=3)C=CC=2)C2C(=CC=CC=2)C=CC=1P(C(C)(C)C)C(C)(C)C.C[C:54]([N:56](C)C)=O>[C-]#N.[C-]#N.[Zn+2].[Zn]>[C:54]([C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@@H:11]3[CH2:15][CH2:14][C@:13]([OH:17])([CH3:16])[C:12]3([CH3:19])[CH3:18])=[C:8]([C:20]([NH2:22])=[O:21])[CH:7]=[N:6][N:5]2[CH:23]=1)#[N:56]

Participants

6

Reactant 3

HCID 31374DimethylacetamideHCID 2734941(1,1'-Binaphthalen)-2-yldi-tert-butylphosphineHCID 86707705HCID 86707705, compound2×

Product 1

HCID 68358872HCID 68358872, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalyst

Conditions

Temperature
90 °C

Procedure

A mixture of 6-bromo-4-((1R,3R)-3-hydroxy-2,2,3-trimethylcyclopentylamino)pyrrolo[1,2-b]-pyridazine-3-carboxamide (Intermediate 51, 18 mg, 0.047 mmol), Zn(CN)2 (3 mg, 0.025 mmol), Pd(COCF3)2 1.6 mg, 0.005 mmol), 1,1′-binaphthyl-2-yldi-tert-butylphosphine (1.9 mg, 0.005 mmol), and zinc (0.62 mg, 0.09 mmol) in DMA (0.2 mL) was purged with N2 then heated at 90° C. for 8 h. The product was isolated via reverse-phase preparative HPLC to afford the title compound (1.1 mg) as a white solid. LCMS: 328.07 (M+H)+; HPLC (condition B): retention time=3.15 min. 1H NMR (MeOD, 400 MHz) δ 8.24 (s, 1H), 8.07 (d, J=1.8 Hz, 1H), 7.48 (d, J=1.8 Hz, 1H), 4.66 (t, J=9.0 Hz, 1H), 2.35 (m, 1H), 2.01 (m, 1H), 1.78 (m, 1H), 1.59 (m, 1H), 1.24 (s, 3H), 1.00 (s, 3H), 0.95 (s, 3H).

Workup

  1. customwas purged with N2
  2. customThe product was isolated via reverse-phase preparative HPLC

Sources & evidence

ORD record
ord-780bec36ae8a4dfc9dd8557f736338d0
Source dataset
uspto-grants-2014_12
Patent number
US08921368B2

Reaction notes

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