N-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzo[d]oxazol-2-amine → 2-{4-amino-3-[4-(1,3-benzoxazol-2-ylamino)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl}-3-pyridyl cyanide

HRID 432430Notes

Reaction equation

HRID 432430 reaction equation
NC1N=CN=C2N(CC(OCC)=O)N=C(C3C=CC(NS(C4C=CC=C(Cl)C=4Cl)(=O)=O)=C(F)C=3)C=12.[O:36]1[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=2[N:38]=[C:37]1[NH:45][C:46]1[CH:51]=[CH:50][C:49](B2OC(C)(C)C(C)(C)O2)=[CH:48][CH:47]=1.[NH2:61][C:62]1[N:67]=[CH:66][N:65]=[C:64]2[N:68]([C:72]3[C:77]([C:78]#[N:79])=[CH:76][CH:75]=[CH:74][N:73]=3)[N:69]=[C:70](I)[C:63]=12>>[NH2:61][C:62]1[N:67]=[CH:66][N:65]=[C:64]2[N:68]([C:72]3[C:77]([C:78]#[N:79])=[CH:76][CH:75]=[CH:74][N:73]=3)[N:69]=[C:70]([C:49]3[CH:48]=[CH:47][C:46]([NH:45][C:37]4[O:36][C:40]5[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=5[N:38]=4)=[CH:51][CH:50]=3)[C:63]=12

Participants

4

Reactant 3

HCID 22346815N-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzo[d]oxazol-2-amineHCID 22346920Ethyl 2-[4-amino-3-(4-{[(2,3-dichlorophenyl)sulfonyl]amino}-3-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]acetateHCID 223470652-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-pyridyl cyanide

Product 1

HCID 223473772-{4-amino-3-[4-(1,3-benzoxazol-2-ylamino)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl}-3-pyridyl cyanideYield 7.3%

Procedure

The procedure for Suzuki coupling, used in the preparation of ethyl 2-[4-amino-3-(4-{[(2,3-dichlorophenyl)sulfonyl]amino}-3-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]acetate, was used to couple N-(1,3-benzoxazol-2-yl)-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]amine (0.052 g, 0.155 mmol) with 2-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-pyridyl cyanide (0.045 g, 0.124 mmol). Purification 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 10.1-11.2 min) afforded 2-{4-amino-3-[4-(1,3-benzoxazol-2-ylamino)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl}-3-pyridyl cyanide as a yellow powder (0.004 g, 0.009 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 8.55 min; MS (MH)+ 446.

Workup

  1. customPurification 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-05396f06e5f74074a8da940c3b0ebd2e
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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