Hydrochloric Acid → HCID 10448320, compound

HRID 1816157Notes

Reaction equation

HRID 1816157 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[N:21]1[C:25](=O)[CH2:24][CH2:23][C:22]1=O.[Cl:28][C:29]1[CH:37]=[C:36]2[C:32]([C:33]([C:41]([OH:43])=O)=[CH:34][N:35]2[CH:38]([CH3:40])[CH3:39])=[CH:31][CH:30]=1.Cl.[NH2:45][C:46]1SC(C)=C(C)N=1.C(N(CC)C(C)C)(C)C.Cl>C(Cl)Cl.O.C(OCC)(=O)C>[N:21]1[CH:25]=[CH:24][CH:23]=[CH:22][C:46]=1[NH:45][C:41]([C:33]1[C:32]2[C:36](=[CH:37][C:29]([Cl:28])=[CH:30][CH:31]=2)[N:35]([CH:38]([CH3:39])[CH3:40])[CH:34]=1)=[O:43]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 81531DiisopropylethylamineHCID 162113874,5-Dimethyl-1,3-thiazol-2-amine--hydrogen chloride (1/1)HCID 224972296-Chloro-1-(propan-2-yl)-1H-indole-3-carboxylic acid

Product 1

HCID 10448320HCID 10448320, compoundYield 244.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (251 mg, 0.82 mmol) in methylene chloride (3 mL) cooled to 0° C. was treated with N-bromosuccinimide (146 mg, 0.82 mmol). This solution was stirred at 0° C. for 15 min. At this time, the reaction was treated with 6-chloro-1-isopropyl-1H-indole-3-carboxylic acid (150 mg, 0.63 mmol). This solution was stirred at 0° C. for 15 min and then was allowed to warm to 25° C. where it was stirred for 30 min. The reaction was then treated with 2-amino-4,5-dimethylthiazole hydrochloride (239 mg, 1.45 mmol) and was stirred at 25° C. for 30 min. The reaction was then treated with N,N-diisopropylethylamine (0.22 mL, 1.26 mmol) and stirred at 25° C. for 2 d. At this time, the reaction was diluted with water (30 mL) and ethyl acetate (30 mL). This mixture was treated with a 1N aqueous hydrochloric acid solution (10 mL). The organic layer was separated and was washed with a saturated aqueous sodium bicarbonate solution (1×25 mL) and a saturated aqueous sodium chloride solution (1×25 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 1/1 hexanes/ethyl acetate) afforded 6-chloro-1-isopropyl-1H-indole-3-carboxylic acid pyridin-2-ylamide (483 mg, 83%) as a yellow solid: mp 149-150° C.; (ES)+-HRMS m/e calcd for C17H16ClN3O (M+Na)+ 336.0874, found 336.0876.

Workup

  1. stirringThis solution was stirred at 0° C. for 15 min
  2. temperatureto warm to 25° C. where it
  3. stirringwas stirred for 30 min
  4. stirringwas stirred at 25° C. for 30 min
  5. stirringstirred at 25° C. for 2 d
  6. customThe organic layer was separated
  7. washwas washed with a saturated aqueous sodium bicarbonate solution (1×25 mL)
  8. dry with materialThe organic layer was dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-840e5834bf004cc7a0f24833b37968b8
Source dataset
uspto-grants-2005_04
Patent number
US06881844B2

Reaction notes

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