Hydrogen Bromide → 4-Cyclohexyl-5-{2-[3-(2-diethylamino-ethylamino)phenylamino]-5-methyl-pyrimidin-4-yl}2-methylsulfanylthiophene-3-carbonitrile

HRID 6861

Reaction equation

HRID 6861 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[C:13]([C:15]3[S:19][C:18]([S:20][CH3:21])=[C:17]([C:22]#[N:23])[C:16]=3[CH:24]3[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]3)[C:12]([CH3:30])=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:31]([N:33]([CH2:37][CH3:38])[CH2:34][CH2:35]Br)[CH3:32].Br.CC(C)([O-])C.[Na+]>C1COCC1.C(Cl)Cl.CO>[CH:24]1([C:16]2[C:17]([C:22]#[N:23])=[C:18]([S:20][CH3:21])[S:19][C:15]=2[C:13]2[C:12]([CH3:30])=[CH:11][N:10]=[C:9]([NH:8][C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][CH2:32][CH2:31][N:33]([CH2:37][CH3:38])[CH2:34][CH3:35])[CH:3]=3)[N:14]=2)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

8

Reactant 4

HCID 260Hydrogen BromideHCID 706082-Bromo-N,N-diethylethanamineHCID 220190265-[2-(3-Aminophenylamino)-5-methyl-pyrimidin-4-yl]-4-cyclohexyl-2-methylsulfanyl-thiophene-3-carbonitrileHCID 23676156Sodium t-butoxide

Product 1

HCID 220190444-Cyclohexyl-5-{2-[3-(2-diethylamino-ethylamino)phenylamino]-5-methyl-pyrimidin-4-yl}2-methylsulfanylthiophene-3-carbonitrileYield 33%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-[2-(3-aminophenylamino)-5-methyl-pyrimidin-4-yl]-4-cyclohexyl-2-methylsulfanyl-thiophene-3-carbonitrile (20 mg, 45.91 micromol) and N,N-diethyl-2-aminobromoethane.HBr (12 mg, 45.91 micromol) in THF was added sodium t-butoxide (9 mg, 91.82 micromol) and the reaction was stirred at ambient temperature overnight. TLC indicated conversion to product (10% MeOH:CH2Cl2). The reaction was partitioned between EtOAc and water, the organics were dried over sodium sulfate then concentrated in vacuo. The crude product was purified by chromatography (silica gel, 5% MeOH:CH2Cl2) to afford VI-26 in 33% yield. δ 0.95 (bs, 6H), 1.0–1.8 (m, 10H), 2.0 (s, 3H), 2.6 (s, 3H), 2.75 (bs, 2H), 3.4 (s, 1H), 3.6 (bs, 2H), 4.0 (bs, 2H), 5.2 (s, 1H), 6.5 (d, 1H), 6.55 (s, 1H), 6.6 (d, 1H), 7.0 (t, 1H), 8.1 (s, 1H).

Workup

  1. customThe reaction was partitioned between EtOAc and water
  2. dry with materialthe organics were dried over sodium sulfate
  3. concentrationthen concentrated in vacuo
  4. customThe crude product was purified by chromatography (silica gel, 5% MeOH:CH2Cl2)
  5. customto afford VI-26 in 33% yield

Sources & evidence

ORD record
ord-49d09abfa3ef48e594e043221a405f61
Source dataset
uspto-grants-2006_08
Patent number
US07084159B2

Linked notes

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