HCID 67019715, compound → HCID 86725118, compound

HRID 634291Notes

Reaction equation

HRID 634291 reaction equation
[CH:1]([NH:4][C:5]1[O:6][C:7]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[N:15]([S:19]([C:22]2[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=2)(=[O:21])=[O:20])[CH:14]=[C:13]3B2OC(C)(C)C(C)(C)O2)=[N:8][N:9]=1)([CH3:3])[CH3:2].Br[C:39]1[S:40][C:41]([C:44]([NH:46][CH:47]2[CH2:49][CH2:48]2)=[O:45])=[CH:42][N:43]=1.ClC1SC(C(NC2CC2)=O)=CN=1>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.O>[CH:47]1([NH:46][C:44]([C:41]2[S:40][C:39]([C:13]3[C:12]4[C:16](=[CH:17][CH:18]=[C:10]([C:7]5[O:6][C:5]([NH:4][CH:1]([CH3:3])[CH3:2])=[N:9][N:8]=5)[CH:11]=4)[N:15]([S:19]([C:22]4[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=4)(=[O:20])=[O:21])[CH:14]=3)=[N:43][CH:42]=2)=[O:45])[CH2:48][CH2:49]1

Participants

6

Reactant 3

HCID 67019715HCID 67019715, compoundHCID 68328139HCID 68328139, compoundHCID 68328163HCID 68328163, compound

Product 1

HCID 86725118HCID 86725118, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of N-isopropyl-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (150 mg, 0.287 mmol), 78 mg of the 1:1 mixture of 2-bromo-N-cyclopropylthiazole-5-carboxamide and 2-chloro-N-cyclopropylthiazole-5-carboxamide, Pd2(dba)3 (Strem Chemicals, 8 mg, 8.6 μmol), Xphos (Stem Chemicals, cat #15-1152, 9 mg, 17 μmol), potassium phosphate (183 mg, 0.861 mmol) in dioxane (2.5 mL) and water (0.5 mL) was heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 130° C. for 25 min. LCMS indicated the presence of desired product (M+1=563.0), as well as a significant amount of the starting N-isopropyl-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine. To the reaction mixture was added Pd(PPh3)4 (Strem Chemicals, cat #46-2150, 10 mg) and 50 mg of the 1:1 mixture of 2-bromo-N-cyclopropylthiazole-5-carboxamide and 2-chloro-N-cyclopropylthiazole-5-carboxamide. It was heated again at 130° C. for 15 min in an Initiator microwave reactor. The reaction mixture was treated with water (5 mL) and extracted with EtOAc (2×25 mL). The organic extracts were washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by silica gel flash chromatography using a gradient of 20-100% EtOAc in hexanes to give N-cyclopropyl-2-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1-tosyl-1H-indol-3-yl)thiazole-5-carb oxamide (60 mg, in 75% purity) as a brown amorphous solid. MS (ESI, pos. ion) m/z: 563.0 (M+1).

Workup

  1. additionTo the reaction mixture was added
  2. extractionextracted with EtOAc (2×25 mL)
  3. washThe organic extracts were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-d74592c715e7439db335af29415079e7
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

Loading…