Cesium fluoride → HCID 136378660, compound

HRID 1520082Notes

Reaction equation

HRID 1520082 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5](=[O:8])[N:4]([CH2:9][C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[N:15](C(OC(C)(C)C)=O)[N:14]=[C:13]3[C:26]2[N:27]=[N:28][N:29]([C:31]3[CH:36]=[CH:35][C:34]([C:37]([N:39]4[CH2:44][CH2:43][O:42][CH2:41][CH2:40]4)=[O:38])=[CH:33][CH:32]=3)[CH:30]=2)[N:3]=1.[OH:45][C:46]1[CH:51]=[CH:50][C:49](B(O)O)=[CH:48][CH:47]=1.[F-].[Cs+]>CN(C=O)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[OH:45][C:46]1[CH:51]=[CH:50][C:49]([C:2]2[CH:7]=[CH:6][C:5](=[O:8])[N:4]([CH2:9][C:10]3[CH:11]=[C:12]4[C:16](=[CH:17][CH:18]=3)[NH:15][N:14]=[C:13]4[C:26]3[N:27]=[N:28][N:29]([C:31]4[CH:36]=[CH:35][C:34]([C:37]([N:39]5[CH2:44][CH2:43][O:42][CH2:41][CH2:40]5)=[O:38])=[CH:33][CH:32]=4)[CH:30]=3)[N:3]=2)=[CH:48][CH:47]=1

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 27343604-Hydroxyphenylboronic acidHCID 67981111HCID 67981111, compound

Product 1

HCID 136378660HCID 136378660, compoundYield 12%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A suspension of PdCl2(PPh3)2 (10 mg; 0.01 mmol; 0.11 eq.), tert-butyl 5-[(3-chloro-6-oxopyridazin-1(6H)-yl)methyl]-3-{1-[4-(morpholin-4-ylcarbonyl)phenyl]-1H-1,2,3-triazol-4-yl}-1H-indazole-1-carboxylate (79 mg; 0.13 mmol; 1.0 eq.), 4-hydroxyphenylboronic acid (35 mg; 0.25 mmol; 2.0 eq.) and cesium fluoride (65 mg; 0.43 mmol; 3.3 eq.) in DMF (2.0 mL) and water (1.0 mL) was degassed with argon in a sealed tube and heated in MW at 120° C. for 1.5 h. The mixture was then filtered through a celite pad. The filtrate was diluted with EtOAc. The phases were separated and organic phase was washed with a 1 N solution of HCl, dried over magnesium sulfate, filtered and concentrated. Purification of the crude by preparative HPLC gave the title compound as a white solid (9 mg, 9%). 1H NMR (300 MHz, DMSO-d6) δ 13.40 (s, 1H), 9.85 (br, 1H), 9.38 (s, 1H), 8.46 (s, 1H), 8.18-8.12 (m, 2H), 7.98 (d, J=9.8 Hz, 1H), 7.76 (d, J=8.7 Hz, 2H), 7.69 (d, J=8.6 Hz, 2H), 7.59 (d, J=8.6 Hz, 1H), 7.54-7.46 (m, 1H), 7.05 (d, J=9.7 Hz, 1H), 6.85 (d, J=8.7 Hz, 2H), 5.46 (s, 2H), 3.75-3.43 (m, 8H). HPLC (max plot) 98.6%; Rt 3.14 min. UPLC/MS: (MS+) 575.1, (MS−) 573.0.

Workup

  1. customwas degassed with argon in a sealed tube
  2. filtrationThe mixture was then filtered through a celite pad
  3. additionThe filtrate was diluted with EtOAc
  4. customThe phases were separated
  5. washorganic phase was washed with a 1 N solution of HCl
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the crude by preparative HPLC

Sources & evidence

ORD record
ord-5b7ac4dc407f45bcbbe82990d99c3ce3
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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