Diisopropylethylamine → HCID 68156905, compound

HRID 243494Notes

Reaction equation

HRID 243494 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH2:12])[CH3:11])[N:7]([CH2:13][CH2:14][O:15][CH3:16])[C:6]=2[C:17]=1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1.[NH2:24][C:25]1[C:30]([C:31]#[N:32])=[C:29](Cl)[N:28]=[CH:27][N:26]=1.CCN(C(C)C)C(C)C>CC(O)C>[NH2:24][C:25]1[C:30]([C:31]#[N:32])=[C:29]([NH:12][C@H:10]([C:8]2[N:7]([CH2:13][CH2:14][O:15][CH3:16])[C:6]3[C:17]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=4)=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[N:9]=2)[CH3:11])[N:28]=[CH:27][N:26]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 122782624-Amino-6-chloropyrimidine-5-carbonitrileHCID 68156978HCID 68156978, compound

Product 1

HCID 68156905HCID 68156905, compoundYield 63.7%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (S)-1-[6-fluoro-1-(2-methoxyethyl)-7-pyridin-2-yl-1H-benzoimidazol-2-yl]ethylamine (167 mg, 0.53 mmol), 4-amino-6-chloropyrimidine-5-carbonitrile (86 mg, 0.56 mmol) and DIPEA (0.28 mL, 1.6 mmol) in IPA (1 mL) was heated 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 was purified by column chromatography (Si—PPC, gradient 0-10% 2M NH3 in MeOH/DCM) to afford 420 as a white solid (146 mg, 63%). LCMS (Method K): RT 3.15 min [M+H]+ 433. 1H NMR (DMSO-d6, 400 MHz): δ 8.73 (1H, ddd, J=5.0, 2.0, 1.0 Hz), 8.03 (1H, s), 7.97 (1H, ddd, J=7.5, 7.5, 2.0 Hz), 7.74 (1H, dd, J=9.0, 5.0 Hz), 7.70-7.66 (2H, m), 7.51 (1H, ddd, J=7.5, 5.0, 1.0 Hz), 7.30 (2H, bs), 7.18 (1H, dd, J=10.5, 9.0), 5.69 (1H, dq, J=6.5, 6.5 Hz), 4.14-4.07 (1H, m), 3.82 (1H, ddd, J=15.0, 5.0, 5.0 Hz), 3.07-2.99 (2H, m), 2.93 (1H, s), 1.59 (3H, d, J=6.5 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 was purified by column chromatography (Si—PPC, gradient 0-10% 2M NH3 in MeOH/DCM)

Sources & evidence

ORD record
ord-b81b3f3cf6fe440d9523e16e72de3c87
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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