Diisopropylethylamine → HCID 53382477, compound

HRID 243438Notes

Reaction equation

HRID 243438 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13]3[CH:14]=[C:15]([F:18])[CH:16]=[CH:17][C:12]=3[N:11]=[C:10]2[C@@H:19]([NH2:21])[CH3:20])[CH:5]=[C:6]([F:8])[CH:7]=1.[NH2:22][C:23]1[C:28]([C:29]#[N:30])=[C:27](Cl)[N:26]=[CH:25][N:24]=1.CCN(C(C)C)C(C)C>CC(O)C.CCOC(C)=O>[NH2:22][C:23]1[C:28]([C:29]#[N:30])=[C:27]([NH:21][C@H:19]([C:10]2[N:9]([C:4]3[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([F:1])[CH:3]=3)[C:13]3[CH:14]=[C:15]([F:18])[CH:16]=[CH:17][C:12]=3[N:11]=2)[CH3:20])[N:26]=[CH:25][N:24]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 122782624-Amino-6-chloropyrimidine-5-carbonitrileHCID 68157272HCID 68157272, compound

Product 1

HCID 53382477HCID 53382477, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (S)-1-[1-(3,5-difluorophenyl)-6-fluoro-1H-benzoimidazol-2-yl]ethylamine (245 mg, 0.84 mmol), 4-amino-6-chloropyrimidine-5-carbonitrile (137 mg, 0.88 mmol) and DIPEA (0.44 mL, 2.5 mmol) in IPA (1.7 mL) was heated in a sealed tube for 16 h at 90° C. After cooling to RT, the volatiles were removed under reduced pressure and the resulting residue loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH, followed by 2M NH3/MeOH. The basic fractions were combined, concentrated in vacuo and the resulting residue purified by column chromatography (Si—PPC, gradient 25-75% EtOAc/cyclohexane) to give colourless oil. The residue was taken up in EtOAc and the product triturated with cyclohexane. The solid was filtered to afford 349 as a white solid (134 mg, 39%). LCMS (Method K): RT 4.10 min [M+H]+ 410. 1H NMR (DMSO-d6, 400 MHz): δ 7.87 (1H, s), 7.76-7.7 (2H, m), 7.36-7.31 (3H, m), 7.18 (2H, bs), 7.13 (1H, ddd, J=10.0, 8.5, 2.5 Hz), 7.05 (1H, dd, J=9.0, 2.5 Hz), 5.64 (1H, dq, J=7.0, 7.0 Hz), 1.56 (3H, d, J=7.0 Hz)

Workup

  1. temperatureAfter cooling to RT
  2. customthe volatiles were removed under reduced pressure
  3. washThe cartridge was washed with MeOH
  4. concentrationconcentrated in vacuo
  5. customthe resulting residue purified by column chromatography (Si—PPC, gradient 25-75% EtOAc/cyclohexane)
  6. customto give colourless oil
  7. customthe product triturated with cyclohexane
  8. filtrationThe solid was filtered

Sources & evidence

ORD record
ord-22991006f5394c92aaddb6951b1527d0
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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