tert-Butanol → HCID 21868477, compound

HRID 857436Notes

Reaction equation

HRID 857436 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3]1[C:4]([Cl:10])=[N:5][C:6](Cl)=[N:7][CH:8]=1.C(O)(C)(C)C.[NH2:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][C:23](=[O:28])[C:22]2([F:30])[F:29].C(N(CC)CC)C>C(O)(C)(C)C.ClCCCl.[Cl-].[Zn+2].[Cl-].C(OCC)C.ClCCCl>[Cl:10][C:4]1[C:3]([C:2]([F:12])([F:11])[F:1])=[CH:8][N:7]=[C:6]([NH:18][C:19]2[CH:20]=[C:21]3[C:25](=[CH:26][CH:27]=2)[NH:24][C:23](=[O:28])[C:22]3([F:30])[F:29])[N:5]=1

Participants

9

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 21868607813424-17-8

Product 1

HCID 21868477HCID 21868477, compoundYield 31%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 111,2-DichloroethaneSolventHCID 3283Diethyl EtherSolventHCID 21868497Tert-butyl alcohol 1,2-dichloroethaneSolvent

Procedure

316 mg (1.46 mmol) 5-trifluoromethyl-2,4-dichloropyrimidine was taken into 2.30 mL of a 1:1 mix of tert-butanol and 1,2-dichloroethane. To this solution was added 1.46 mL (1.46 mmol) zinc chloride solution (1.0 M in ether). The reaction solution was allowed to stir at ambient temperature for thirty minutes. 1.31 mmol 5-Amino-3,3-difluoro-1,3-dihydro-indol-2-one was added drop-wise as a suspension in 500 □L tert-butanol/1,2-dichloroethane solvent mixture. 202 □L (1.46 mmol) triethylamine was slowly added to the slurry. A slight exotherm and severe clumping was noted (Too much diethyl ether to allow for solution). Allowed the reaction mixture to stir at ambient temperature overnight (16 hours). A complete solution had been achieved over the period. All volatiles were removed under reduced pressure to reveal a brown foam. Triteration from methanol gave the titled compound as a tan solid upon filtration in 31% yield (164 mg, 0.450 mmol). APCI m/z 365.2/367.2 (MH+); 1H NMR (D6-DMSO) δ 11.17 (s, 1 exchangeable H), 10.73 (s, 1 exchangeable H), 8.80 (bs, 1 H), 8.00 (bs, 1 H), 7.69 (d, J=8.3 Hz, 1H), 6.99 (d, J=8.3 Hz, 1 H) ppm.

Workup

  1. stirringAllowed the reaction mixture to stir at ambient temperature overnight (16 hours)
  2. customAll volatiles were removed under reduced pressure

Sources & evidence

ORD record
ord-cc7d398e54754a27a47e00c920035e7b
Source dataset
uspto-grants-2006_12
Patent number
US07145008B2

Reaction notes

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