Hydrochloric Acid → HCID 67981486, compound

HRID 1520065Notes

Reaction equation

HRID 1520065 reaction equation
CC(OC(/N=N/C(OC(C)C)=O)=O)C.O[CH2:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[N:21]=[C:20]2[C:33]1[N:34]=[N:35][N:36]([C:38]2[CH:43]=[CH:42][C:41]([C:44]([N:46]3[CH2:51][CH2:50][O:49][CH2:48][CH2:47]3)=[O:45])=[CH:40][CH:39]=2)[CH:37]=1.[N:52]1[NH:53][C:54](=[O:58])[CH:55]=[CH:56][CH:57]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl>C(Cl)Cl>[N:46]1([C:44]([C:41]2[CH:42]=[CH:43][C:38]([N:36]3[CH:37]=[C:33]([C:20]4[C:19]5[C:23](=[CH:24][CH:25]=[C:17]([CH2:16][N:53]6[C:54](=[O:58])[CH:55]=[CH:56][CH:57]=[N:52]6)[CH:18]=5)[N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[N:21]=4)[N:34]=[N:35]3)=[CH:39][CH:40]=2)=[O:45])[CH2:47][CH2:48][O:49][CH2:50][CH2:51]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 681533(2H)-PyridazinoneHCID 5363146Diisopropyl azodicarboxylateHCID 67981415HCID 67981415, compound

Product 1

HCID 67981486HCID 67981486, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

DIAD (0.30 mL; 1.54 mmol; 2.3 eq.) was added dropwise over 1 min to a solution of tert-butyl 5-(hydroxymethyl)-3-{1-[4-(morpholin-4-ylcarbonyl)phenyl]-1H-1,2,3-triazol-4-yl}-1H-indazole-1-carboxylate (340 mg; 0.67 mmol; 1.0 eq.), 3(2H)-pyridazinone (100 mg; 1.04 mmol; 1.5 eq.) and triphenylphosphine (354 mg; 1.35 mmol; 2.0 eq.) in DCM (15 mL). The reaction mixture was stirred for 4 h at RT then poured into HCl (0.1N solution) and extracted with DCM. Combine organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude was purified by flash chromatography on silica (gradient 20:80 to 90:10, MeOH pure) to give the title compound as a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 9.61 (s, 1H), 8.52 (s, 1H), 8.19 (d, J=8.6 Hz, 2H), 8.13 (d, J=8.7 Hz, 1H), 7.98 (dd, J=1.6, 3.9 Hz, 1H), 7.77-7.61 (m, 3H), 7.45 (dd, J=3.9 Hz, 1H), 7.01 (dd, J=9.5 Hz, 1.6, 1H), 5.46 (s, 2H), 3.76-3.35 (m, 8H), 1.69 (s, 9H). HPLC (Condition A): Rt 3.74 min (purity 91.1%). MS (ESI−): 483.4.

Workup

  1. extractionextracted with DCM
  2. washCombine organic phases were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude was purified by flash chromatography on silica (gradient 20:80 to 90:10, MeOH pure)

Sources & evidence

ORD record
ord-68336333c4c34a808e4bcc10b17d82f6
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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