2-Bromothiazole → HCID 67959986, compound

HRID 1529458Notes

Reaction equation

HRID 1529458 reaction equation
Br[C:2]1[S:3][CH:4]=[CH:5][N:6]=1.[F:7][C@@H:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH2:10][C@H:9]1[O:24][C:25]1[N:30]=[C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=2)[CH:28]=[C:27]([C:41]2[C:49]3[C:44](=[CH:45][CH:46]=[C:47]([Sn](C)(C)C)[CH:48]=3)[N:43]([CH:54]3[CH2:59][CH2:58][CH2:57][CH2:56][O:55]3)[N:42]=2)[N:26]=1>CN(C=O)C.[Cu]I.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>[F:7][C@@H:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[O:15])[CH2:10][C@H:9]1[O:24][C:25]1[N:30]=[C:29]([O:31][CH2:32][C:33]2[CH:34]=[CH:35][C:36]([O:39][CH3:40])=[CH:37][CH:38]=2)[CH:28]=[C:27]([C:41]2[C:49]3[C:44](=[CH:45][CH:46]=[C:47]([C:2]4[S:3][CH:4]=[CH:5][N:6]=4)[CH:48]=3)[N:43]([CH:54]3[CH2:59][CH2:58][CH2:57][CH2:56][O:55]3)[N:42]=2)[N:26]=1

Participants

6

Reactant 2

HCID 764302-BromothiazoleHCID 67960651HCID 67960651, compound

Product 1

HCID 67959986HCID 67959986, compoundYield 22.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 2-bromothiazole (20 mg, 0.12 mmol) and benzyl trans-4-fluoro-3-((4-((4-methoxybenzyl)oxy)-6-(1-(tetrahydro-2H-pyran-2-yl)-5-(trimethylstannyl)-1H-indazol-3-yl)pyrimidin-2-yl)oxy)piperidine-1-carboxylate (racemic) (100 mg, 0.12 mmol) in DMF (1 mL) was bubbled with argon for 15 min. To the above mixture was added CuI (11 mg, 0.060 mmol) and Pd(PPh3)4 (13 mg, 0.012 mmol) and argon gas was bubbled for another 15 min. The reaction was heated at 100 C for 2 h. The reaction was quenched with water and the suspension was filtered. The solid was dried then purified with basic alumina chromatography (eluting with 30% EtOAc in hexanes) to give benzyl trans-4-fluoro-3-((4-((4-methoxybenzyl)oxy)-6-(1-(tetrahydro-2H-pyran-2-yl)-5-(thiazol-2-yl)-1H-indazol-3-yl)pyrimidin-2-yl)oxy)piperidine-1-carboxylate (racemic) (20 mg, 11%) as a off brown solid. MS (ESI, pos. ion) m/z: 750.8 (M+1).

Workup

  1. customwas bubbled for another 15 min
  2. temperatureThe reaction was heated at 100 C for 2 h
  3. customThe reaction was quenched with water
  4. filtrationthe suspension was filtered
  5. customThe solid was dried
  6. customthen purified with basic alumina chromatography (eluting with 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-dbe6c488827646ee85f766bf0cb09eac
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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