Urea → HCID 22347149, compound

HRID 897720Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C:30]3[CH:35]=[CH:34][C:33]([N:36]4[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]4)=[CH:32][C:31]=3[C:43]#[N:44])[N:9]=[C:10](C3C=CC(NS(C4C=CC=C(Cl)C=4Cl)(=O)=O)=C(F)C=3)[C:3]=12.NC(N)=O.NC1N=CN=C2N(CC(OCC)=O)N=C([C:59]3[CH:64]=[CH:63][C:62]([NH:65][C:66]([NH:68][C:69]4[CH:70]=[C:71]([CH3:75])[CH:72]=[CH:73][CH:74]=4)=[O:67])=[C:61]([F:76])[CH:60]=3)C=12.NC1N=CN=C2N(C3C=CC(N4CCN(C)CC4)=CC=3C#N)N=C(C3C=CC(N)=C(F)C=3)C=12.C1(C)C=CC=C(N=C=O)C=1>>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C:30]3[CH:35]=[CH:34][C:33]([N:36]4[CH2:37][CH2:38][N:39]([CH3:42])[CH2:40][CH2:41]4)=[CH:32][C:31]=3[C:43]#[N:44])[N:9]=[C:10]([C:59]3[CH:64]=[CH:63][C:62]([NH:65][C:66]([NH:68][C:69]4[CH:74]=[CH:73][CH:72]=[C:71]([CH3:75])[CH:70]=4)=[O:67])=[C:61]([F:76])[CH:60]=3)[C:3]=12

Participants

Reactant 5

HCID 1176Urea

HCID 69303m-Tolyl isocyanate

HCID 22346765HCID 22346765, compound

HCID 22346864HCID 22346864, compound

HCID 22347079HCID 22347079, compound

Product 1

HCID 22347149HCID 22347149, compound

Procedure

The same procedure used to prepare N1-(4-{4-amino-1-[2-cyano-4-(4-methylpiperazino)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-fluorophenyl)-2,3-dichloro-1-benzenesulfonamide was employed, except that the final step employed the procedure for urea formation used to prepare ethyl 2-(4-amino-3-{3-fluoro-4-[(3-toluidinocarbonyl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)acetate, entailing the reaction of 2-[4-amino-3-(4-amino-3-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-5-(4-methylpiperazino)benzonitrile (0.018 g, 0.041 mmol) with m-tolyl isocyanate (0.005 mL, 0.040 mmol). Purification of the product by preparative HPLC (25 to 100% acetonitrile in 0.1 M aqueous ammonium acetate over 20 min at 21 mL/min using an 8μ Hypersil HS C18, 250×21 mm column, Rt 9.3-10.3 min) afforded N-(4-{4-amino-1-[2-cyano-4-(4-methylpiperazino)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-fluorophenyl)-N′-(3-methylphenyl)urea as a yellow powder (0.008 g, 0.014 mmol); RP-HPLC (25 to 100% acetonitrile in 0.1 M aqueous ammonium acetate over 10 min at 1 mL/min using a 5μ Hypersil HS C18, 250×4.6 mm column) Rt 8.03 min; MS (MH)+ 577.

Workup

customPurification of the product by preparative HPLC (25 to 100% acetonitrile in 0.1 M aqueous ammonium acetate over 20 min at 21 mL/min

Sources & evidence

ORD record: ord-62ee514cf9cb43d383f4bbf3b2addfd8
Source dataset: uspto-grants-2005_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06921763B2

Reaction notes

Loading…