Methylhydrazine → HCID 71244788, compound

HRID 80840Notes

Reaction equation

HRID 80840 reaction equation
[CH:1]1([C:4](=O)[CH2:5][C:6]([N:8]2[CH2:48][CH2:47][C:11]3[N:12]=[C:13]([C:26]4[C:34]([CH3:35])=[CH:33][CH:32]=[C:31]5[C:27]=4[C:28]([CH3:46])=[N:29][N:30]5[S:36]([C:39]4[CH:45]=[CH:44][C:42]([CH3:43])=[CH:41][CH:40]=4)(=[O:38])=[O:37])[N:14]=[C:15]([N:16]4[CH2:21]C[C@@H](OC)[C:18](C)(C)[CH2:17]4)[C:10]=3[CH2:9]2)=O)[CH2:3][CH2:2]1.[CH2:50]1[CH2:54][O:53][CH2:52][CH2:51]1.[CH3:55][NH:56][NH2:57].[CH3:58]OC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=S)=CC=1>N1C=CC=CC=1>[CH:1]1([C:4]2[CH:5]=[C:6]([N:8]3[CH2:48][CH2:47][C:11]4[N:12]=[C:13]([C:26]5[C:34]([CH3:35])=[CH:33][CH:32]=[C:31]6[C:27]=5[C:28]([CH3:46])=[N:29][N:30]6[S:36]([C:39]5[CH:45]=[CH:44][C:42]([CH3:43])=[CH:41][CH:40]=5)(=[O:38])=[O:37])[N:14]=[C:15]([N:16]5[CH2:17][CH2:18][C@@H:54]([O:53][CH3:52])[C:50]([CH3:51])([CH3:58])[CH2:21]5)[C:10]=4[CH2:9]3)[N:56]([CH3:55])[N:57]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 6061MethylhydrazineHCID 8028TetrahydrofuranHCID 87949Lawesson's reagentHCID 86690285(R)-1-cyclopropyl-3-(2-(3,5-dimethyl-1-tosyl-1H-indazol-4-yl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)propane-1,3-dione

Product 1

HCID 71244788HCID 71244788, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
125 °C

Procedure

A microwave vial was charged with (R)-1-cyclopropyl-3-(2-(3,5-dimethyl-1-tosyl-1H-indazol-4-yl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)propane-1,3-dione (0.563 g, 0.82 mmol) and THF (5 mL) and placed under a nitrogen atmosphere. Methyl hydrazine (87 μL, 1.64 mmol), pyridine (0.25 mL) and Lawesson's reagent (0.366 g, 0.90 mmol) were then added in sequence. The vessel was sealed and heated at 125° C. in a microwave reactor for 12 min. At that point the reaction mixture was concentrated and the residue was purified via FCC (0-10% MeOH/DCM; 10% NH4OH in DCM) to obtain the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.56-8.61 (m, 1H), 8.05 (d, J=8.6 Hz, 1 H), 7.79 (d, J=8.3 Hz, 2 H), 7.56 (d, J=8.8 Hz, 1 H), 7.38 (d, J=8.6 Hz, 2 H), 5.52 (s, 1 H), 4.08 (d, J=13.4 Hz, 1 H), 3.96 (d, J=15.4 Hz, 1 H), 3.61-3.69 (m, 1 H), 3.55 (s, 3 H), 3.28-3.31 (m, 2 H), 3.26 (s, 3 H), 3.04 (t, J=10.2 Hz, 1 H), 2.94-2.99 (m, 1 H), 2.82-2.92 (m, 2 H), 2.33 (s, 3 H), 2.19 (s, 3 H), 1.86-1.94 (m, 1 H), 1.83 (s, 3 H), 1.67-1.78 (m, 1 H), 1.45-1.58 (m, 1 H), 0.91 (s, 3 H), 0.74-0.83 (m, 5H), 0.50-0.58 (m, 2 H); MS (ESI+) m/z 695.6 (M+H)+.

Workup

  1. customThe vessel was sealed
  2. concentrationAt that point the reaction mixture was concentrated
  3. customthe residue was purified via FCC (0-10% MeOH/DCM; 10% NH4OH in DCM)

Sources & evidence

ORD record
ord-0536606c9ad24562846f7d551e95a880
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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