Isobutylamine → HCID 59468556, compound

HRID 1012198Notes

Reaction equation

HRID 1012198 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:15]=[C:16]([CH:20]([OH:22])[CH3:21])[CH:17]=[CH:18][CH:19]=3)[N:8]=2)[S:5][CH:6]=1.[CH2:23]([NH2:27])[CH:24]([CH3:26])[CH3:25].C1C[O:31][CH2:30]C1.C1CCN2C(=NCCC2)CC1>CS(C)=O.[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo]>[CH2:23]([NH:27][C:30]([C:2]1[CH:3]=[C:4]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([CH:20]([OH:22])[CH3:21])[CH:15]=3)[N:8]=2)[S:5][CH:6]=1)=[O:31])[CH:24]([CH3:26])[CH3:25]

Participants

7

Reactant 4

HCID 6558IsobutylamineHCID 8028TetrahydrofuranHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 59468582HCID 59468582, compound

Product 1

HCID 59468556HCID 59468556, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 98885Molybdenum carbonyl (Mo(CO)6)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
150 °C

Procedure

A 5 mL Personal Chemistry™ microwave vial was charged with 1-{3-[4-(4-Bromo-thiophen-2-yl)-pyrimidin-2-ylamino]-phenyl}-ethanol (149.3 mg, 0.40 mmol, prepared according to Method 22), isobutylamine (120 uL, 1.20 mmol), molybdenum hexacarbonyl (109.2 mg, 0.41 mmol), THF (2 mL), 20 mg (0.02 mmol) of Hermann's Palladacycle [trans-di-mu-acetatobis[2-9di-O-tolylphpsphino)benzyl]dipalladium(II)], and DBU (180 uL, 1.20 mmol). The reaction mixture was heated to 150° C. in a microwave reactor for 15 min. The crude reaction mixture was diluted with DMSO (2 mL), filtered through a plug of silica gel, then purified by mass-triggered reverse-phase HPLC, (C-18; eluting with a 5-95% gradient consisting of 0.1% formic acid in water: 0.1% formic acid in ACN). Lyophilization of the purified fraction provided 39.5 mg (25% yield) of 5-{2-[3-(1-Hydroxy-ethyl)-phenylamino]-pyrimidin-4-yl}-thiophene-3-carboxylic acid isobutyl-amide as a white powder. 1H NMR (d6-DMSO) δ 9.49 (br. s, 1H), 8.34 (d, J=5.0 Hz, 1H), 8.20 (t, J=6.0 Hz, 1H), 8.16 (dd, J=6.0, 0.5 Hz, 1H), 7.67 (br.s, 1H), 7.49 (dd, J=5.0, 1.2 Hz, 1H), 7.15 (d, J=5.0 Hz, 1H), 7.09 (t, J=7.5 Hz, 1H), 6.80 (d, J=7.5 Hz, 1H), 4.97 (br.d, J=3.5 Hz, 1H), 4.55 (qrt, J=5.5 Hz, 1H), 2.91 (t, J=6.5 Hz, 2H), 1.67 (m, 1H), 1.19 (d, J=6.0 Hz, 3H), 0.74 (d, J=7.0 Hz, 6H); HPLC/MS m/z: 397 [MH]+.

Workup

  1. customThe crude reaction mixture
  2. filtrationfiltered through a plug of silica gel
  3. custompurified by mass-triggered reverse-phase HPLC
  4. washeluting with a 5-95%

Sources & evidence

ORD record
ord-4635939cc6604ae892b6a3881575751e
Source dataset
uspto-grants-2011_07
Patent number
US07977481B2

Reaction notes

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