3-Methoxyphenyl isocyanate → HCID 178491216, compound

HRID 432238Notes

Reaction equation

HRID 432238 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[N:14][C:15]=3[NH2:17])[N:10]([C@H:18]3[CH2:23][CH2:22][C@H:21]([N:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[CH2:20][CH2:19]3)[N:9]=2)=[CH:4][C:3]=1[F:31].[CH3:32][O:33][C:34]1[CH:35]=[C:36]([N:40]=[C:41]=[O:42])[CH:37]=[CH:38][CH:39]=1>N1C=CC=CC=1>[NH2:17][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[N:10]([C@H:18]3[CH2:23][CH2:22][C@H:21]([N:24]4[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]4)[CH2:20][CH2:19]3)[N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:41]([NH:40][C:36]4[CH:37]=[CH:38][CH:39]=[C:34]([O:33][CH3:32])[CH:35]=4)=[O:42])=[C:3]([F:31])[CH:4]=3)[C:16]=12

Participants

4

Reactant 2

HCID 878433-Methoxyphenyl isocyanateHCID 178480988HCID 178480988, compound

Product 1

HCID 178491216HCID 178491216, compoundYield 73.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

trans-3-(4-Amino-3-fluorophenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (77 mg, 0.182 mmol) was suspended in pyridine (1 mL). A solution of 3-methoxyphenylisocyanate (30 mg, 0.200 mmol) in pyridine (1 mL) was added to the reaction mixture and stirring was continued for 19 hours. The reaction mixture was concentrated under reduced pressure to yield the crude product as a pale yellow oil (149 mg). The crude material was purified on 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) to afford trans-N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-fluorophenyl)-N′-(3-methoxyphenyl)urea as a white solid (76 mg, 0.133 mmol). HPLC-RT: 12.33 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+)=574.2.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto yield the crude product as a pale yellow oil (149 mg)
  3. customThe crude material was purified on 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)

Sources & evidence

ORD record
ord-befaab79236f443ca10d1087d3edfd4e
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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