HCID 68181646, compound → HCID 68181829, compound

HRID 1398626Notes

Reaction equation

HRID 1398626 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14](I)[CH:15]=3)[C:10]([C:18]([OH:20])=[O:19])=[N:9]2)[C:5]([Cl:21])=[CH:4][N:3]=1.[CH3:22][C:23]1[O:27][N:26]=[C:25]([C@:28]([OH:32])([C:30]#[CH:31])[CH3:29])[N:24]=1>N1CCCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:31]#[C:30][C@@:28]([OH:32])([C:25]4[N:24]=[C:23]([CH3:22])[O:27][N:26]=4)[CH3:29])[CH:15]=3)[C:10]([C:18]([OH:20])=[O:19])=[N:9]2)[C:5]([Cl:21])=[CH:4][N:3]=1

Participants

6

Reactant 2

HCID 68181646HCID 68181646, compoundHCID 86669593(R)-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol

Product 1

HCID 68181829HCID 68181829, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8082PiperidineSolvent

Conditions

Temperature
35 °C

Procedure

To a solution of 1-(2-amino-5-chloropyrimidin-4-yl)-6-iodo-1H-indazole-3-carboxylic acid (400 mg at 58% purity, 0.56 mmol) in piperidine (3 mL) was introduced tetrakis(triphenylphosphine)palladium (0) (111 mg, 0.10 mmol), copper(I) iodide (18.3 mg, 0.10 mmol) and (2R)-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol (293 mg, 1.93 mmol). The reaction was warmed to 35° C. under an atmosphere of nitrogen for 1 hr. After cooling to RT, the reaction mixture was concentrated in vacuo and the residue purified by silica gel flash column chromatography (eluent: DCM containing a 1-15% MeOH gradient followed by 85:15 DCM:7M ammonia in methanol). The partially purified compound was dissolved in DCM (20 mL) and washed with 2M aqueous citric acid (10 mL). The organic phase was dried (Na2SO4), filtered and concentrated in vacuo to furnish the title compound as a dark oil: 1H NMR (500 MHz, DMSO) delta 1.86 (3H, s), 2.62 (3H, s), 6.80 (1H, s), 7.53-7.35 (3H, m), 8.09 (1H, s), 8.23 (1H, d, J=8.4 Hz), 8.56 (1H, s); LC-MS: m/z=+439.90/441.90 (M+H)+. This compound, with LC-MS purity=61% UV, was used in the next step without further purification.

Workup

  1. temperatureAfter cooling to RT
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. customthe residue purified by silica gel flash column chromatography (eluent
  4. dissolutionThe partially purified compound was dissolved in DCM (20 mL)
  5. washwashed with 2M aqueous citric acid (10 mL)
  6. dry with materialThe organic phase was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fd3d8d09b6f941d48e465ee39f4f9002
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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