Diisopropylethylamine → HCID 68158145, compound

HRID 243422Notes

Reaction equation

HRID 243422 reaction equation
Cl.Cl.[NH2:3][C@H:4]([C:6]1[N:7]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:8]2[C:14]([C:15]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[O:16])=[C:13]([F:23])[CH:12]=[CH:11][C:9]=2[N:10]=1)[CH3:5].[NH2:30][C:31]1[C:36]([C:37]#[N:38])=[C:35](Cl)[N:34]=[CH:33][N:32]=1.CCN(C(C)C)C(C)C>CC(O)C>[NH2:30][C:31]1[C:36]([C:37]#[N:38])=[C:35]([NH:3][C@H:4]([C:6]2[N:7]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:8]3[C:14]([C:15]([N:17]4[CH2:18][CH2:19][O:20][CH2:21][CH2:22]4)=[O:16])=[C:13]([F:23])[CH:12]=[CH:11][C:9]=3[N:10]=2)[CH3:5])[N:34]=[CH:33][N:32]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 122782624-Amino-6-chloropyrimidine-5-carbonitrileHCID 68157708HCID 68157708, compound

Product 1

HCID 68158145HCID 68158145, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of [2-((S)-1-aminoethyl)-5-fluoro-3-phenyl-3H-benzoimidazol-4-yl]-morpholin-4-ylmethanone dihydrochloride (300 mg, 0.69 mmol) in IPA (5 mL) was added 4-amino-6-chloropyrimidine-5-carbonitrile (108 mg, 0.69 mmol) and DIPEA (353 mL, 2.07 mmol) and the reaction mixture heated at 90° C. for 16 h. The reaction mixture was concentrated in vacuo and the resultant residue subjected to flash chromatography (SiO2, eluting with 0-4% methanol in EtOAc). The product was triturated with diethyl ether. The solid obtained was purified by prep HPLC (C18 Phenomenex column, 10-90% MeCN in water 0.1% formic acid, 20 min gradient) to give the title compound as a white solid (140 mg, 42%). 1H NMR 400 MHz δ (DMSO-d6) (mixture of rotamers): 7.80 (0.5H, s), 7.76 (0.5H, s), 7.73 (1H, dd, J=8.8, 4.8 Hz), 7.67 (0.5H, d, J=7.5 Hz), 7.54 (0.5H, d, J=7.2 Hz), 7.50-7.31 (5H, m), 7.19-7.07 (3H, m), 5.28 (0.5H, quin, J=7.1 Hz), 5.21 (0.5H, quin, J=7.0 Hz), 3.48-3.35 (1H, m), 3.34-3.18 (4H, m), 3.10-2.87 (2H, m), 2.56-2.47 (1H, m), 1.47-1.40 (3H, m), LCMS (Method K): RT=2.96 min, [M+H]+=487, RT=3.00 min, [M+H]+=487 (mixture of rotamers)

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. washthe resultant residue subjected to flash chromatography (SiO2, eluting with 0-4% methanol in EtOAc)
  3. customThe product was triturated with diethyl ether
  4. customThe solid obtained
  5. customwas purified by prep HPLC (C18 Phenomenex column, 10-90% MeCN in water 0.1% formic acid, 20 min gradient)

Sources & evidence

ORD record
ord-276517ea46bf4a268802a019b1acd3f0
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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