m-Tolyl isocyanate → HCID 178465295, compound

HRID 432240Notes

Reaction equation

HRID 432240 reaction equation
[CH2:1]([NH:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[N:16][C:17]=3[NH2:19])[N:12]([C@H:20]3[CH2:25][CH2:24][C@@H:23]([N:26]4[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]4)[CH2:22][CH2:21]3)[N:11]=2)=[CH:6][C:5]=1[F:33])[CH3:2].[C:34]1([CH3:43])[CH:39]=[CH:38][CH:37]=[C:36]([N:40]=[C:41]=[O:42])[CH:35]=1>N1C=CC=CC=1>[NH2:19][C:17]1[N:16]=[CH:15][N:14]=[C:13]2[N:12]([C@H:20]3[CH2:25][CH2:24][C@@H:23]([N:26]4[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]4)[CH2:22][CH2:21]3)[N:11]=[C:10]([C:7]3[CH:8]=[CH:9][C:4]([N:3]([CH2:1][CH3:2])[C:41]([NH:40][C:36]4[CH:37]=[CH:38][CH:39]=[C:34]([CH3:43])[CH:35]=4)=[O:42])=[C:5]([F:33])[CH:6]=3)[C:18]=12

Participants

4

Reactant 2

HCID 69303m-Tolyl isocyanate2×HCID 178463264HCID 178463264, compound

Product 1

HCID 178465295HCID 178465295, compoundYield 106.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

cis-3-[4-(Ethylamino)-3-fluorophenyl]-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (80 mg, 0.177 mmol) was dissolved in pyridine (3 mL) then cooled to 0° C. m-Tolylisocyanate (26 mg, 0.194 mmol) was added to the reaction and stirring was continued at 0° C. for 2.5 hours. The reaction mixture was warmed to room temperature and stirred overnight. Additonal m-tolylisocyanate (13 mg, 0.101 mmol) was added to the reaction mixture and stirring was continued for 1 week. The reaction mixture was concentrated under reduced pressure to give the crude product as a light yellow oil (110 mg). Purification was achieved by RP-HPLC (Waters PrepLC 4000, flow rate: 10 mL/min. λ=254 nm Gradient: 10% to 30% acetonitrile/0.1M aqueous ammonium acetate gradient over 40 minutes; Deltapak C18, 300A, 15 μm, 40×100 mm column). cis-N-(4-{4-Amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-fluorophenyl)-N-ethyl-N′-(3-methylphenyl)urea was collected as a white solid (10 mg). HPLC-RT: 13.18 min. (flow rate: 1 mL/min λ=254 nm Gradient: 5% to 85% acetonitrile/0.1M aqueous ammonium acetate gradient over 20 min.; Deltapak C18, 300A, 5 μm, 150×3.9 mm column); m/z (MH+)=586.5.

Workup

  1. additionwas added to the reaction
  2. stirringstirred overnight
  3. stirringstirring
  4. waitwas continued for 1 week
  5. concentrationThe reaction mixture was concentrated under reduced pressure

Sources & evidence

ORD record
ord-ace3896a286b45efb14f7f8174e09a29
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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