1-Butanol → HCID 178428248, compound

HRID 1091819Notes

Reaction equation

HRID 1091819 reaction equation
[CH3:1][C:2]1[CH:6]=[C:5]([NH:7][C:8]2[CH:13]=[C:12](Cl)[N:11]=[C:10]([S:15][C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([CH:25]4[CH2:27][CH2:26]4)=[O:24])=[CH:18][C:17]=3[F:28])[N:9]=2)[NH:4][N:3]=1.Cl.C[CH2:31][N:32](C(C)C)[CH:33](C)C.[CH2:39]([OH:43])[CH2:40][CH2:41][CH3:42]>CCOC(C)=O>[CH3:1][C:2]1[CH:6]=[C:5]([NH:7][C:8]2[CH:13]=[C:12]([N:32]3[CH2:33][C:39]([CH:40]4[CH2:42][CH2:41]4)([OH:43])[CH2:31]3)[N:11]=[C:10]([S:15][C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([CH:25]4[CH2:27][CH2:26]4)=[O:24])=[CH:18][C:17]=3[F:28])[N:9]=2)[NH:4][N:3]=1

Participants

6

Reactant 4

HCID 2631-ButanolHCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 178428222HCID 178428222, compound

Product 1

HCID 178428248HCID 178428248, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of N-(4-(4-(3-methyl-1H-pyrazol-5-ylamino)-6-chloropyrimidin-2-ylthio)-3-fluorophenyl)cyclopropane-carboxamide (160 mg, 0.38 mmol), 3-cycloropylazetidin-3-ol hydrochloride (70 mg, 0.49 mmol) and DIPEA (0.20 ml) in n-butanol (1.5 ml) were heated in microwave at 130° C. for 1 h. Reaction mixture was then cooled to room temperature, diluted with EtOAc (20 ml), washed with sat NaHCO3 solution (10 ml), water (2×10 ml), brine (10 ml), dried (MgSO4), filtered and evaporated in vacuo. Crude product was purified by flash chromatography on silica (EtOAc/Petrol 30 to 80%) to give the title compound as a white solid (55 mg, 29%). 1H NMR (DMSO-d6) 0.33-0.36 (2H, m), 0.42-0.48 (2H, m), 0.82-0.86 (4H, m), 1.21-1.24 (2H, m), 1.85-1.89 (1H, m), 2.08 (3H, s), 2.10-2.15 (1H, m), 3.66-3.75 (4H, m), 5.42 (1H, br s), 5.67 (1H, 1H, s), 5.8 (1H, br s), 7.42 (1H, d), 7.52-7.58 (1H, m), 7.75 (1H, d), 9.27 (1H, s), 10.65 (1H, s), 11.9 (1H, br s). ES+ 496.90.

Workup

  1. customReaction mixture
  2. temperaturewas then cooled to room temperature
  3. washwashed
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customCrude product was purified by flash chromatography on silica (EtOAc/Petrol 30 to 80%)

Sources & evidence

ORD record
ord-2305285031d54501b151df04ce9b1ccd
Source dataset
uspto-grants-2012_03
Patent number
US08129399B2

Reaction notes

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