Tetrahydrofuran → HCID 70656324, compound

HRID 872938Notes

Reaction equation

[Cl:1][C:2]1[C:3]([CH3:31])=[C:4]([C:10]2[CH:14]=[CH:13][N:12]([CH2:15][C@@H:16]([NH:18][C:19]([C:21]3[N:22]=[C:23](C(OCC)=O)[S:24][CH:25]=3)=[O:20])[CH3:17])[N:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[CH3:32][Mg]Br.[Cl-].[NH4+].[CH2:37]1[CH2:41][O:40]CC1>CCOCC.O.C(Cl)Cl>[Cl:1][C:2]1[C:3]([CH3:31])=[C:4]([C:10]2[CH:14]=[CH:13][N:12]([CH2:15][C@@H:16]([NH:18][C:19]([C:21]3[N:22]=[C:23]([C:41]([OH:40])([CH3:37])[CH3:32])[S:24][CH:25]=3)=[O:20])[CH3:17])[N:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]

Participants

Conditions

Temperature: -78 °C

Procedure

(S)-ethyl 4-(1-(3-(3-chloro-4-cyano-2-methylphenyl)-1H-pyrazol-1-yl)propan-2-ylcarbamoyl)thiazole-2-carboxylate (0.28 g, 0.611 mmol) was dissolved in dry THF under nitrogen atmosphere. The solution was cooled to −78° C. with acetone-dry ice-bath. Methylmagnesium bromide, 3 M solution in Et2O (0.408 ml, 1.223 mmol), was added dropwise. The reaction mixture was stirred in RT overnight. Next day the mixture was again cooled to −78° C. and 1.019 ml of methylmagnesium bromide, 3 M solution in Et2O, was added. The mixture was stirred in RT overnight. Saturated ammonium chloride was added and the mixture was diluted with water and DCM. The organic phase was washed with brine and water. The product was purified by Flash-chromatography. Yield 19.08%. 1H-NMR (400 MHz; CDCl3): δ 1.28 (d, 3H), 1.58 (s, 6H), 2.54 (s, 3H), 2.63 (s, 1H), 4.34 (dd, 1H), 4.44 (dd, 1H), 4.60 (m, 1H), 6.43 (d, 1H), 7.52 (m, 3H), 7.83 (d, 1H), 8.00 (s, 1H).

Workup

temperatureNext day the mixture was again cooled to −78° C.
stirringThe mixture was stirred in RT overnight
washThe organic phase was washed with brine and water
customThe product was purified by Flash-chromatography

Sources & evidence

ORD record: ord-cae553655b2e4b0eb065f19cb1812ad0
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08975254B2

Reaction notes

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