HCID 22346820, compound → HCID 22347313, compound

HRID 432376Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:30][C:31]([O:33]C)=[O:32])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][S:18]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:22]=4[Cl:28])(=[O:20])=[O:19])=[C:13]([F:29])[CH:12]=3)[C:3]=12>CO.O>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:30][C:31]([OH:33])=[O:32])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][S:18]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:22]=4[Cl:28])(=[O:19])=[O:20])=[C:13]([F:29])[CH:12]=3)[C:3]=12

Participants

Conditions

Temperature: 90 °C

Procedure

In a resealable Schlenk flask, methyl 2-[4-amino-3-(4-{[(2,3-dichlorophenyl)sulfonyl]amino}-3-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]acetate (0.030 g, 0.057 mmol) was dissolved in methanol/water (1:1, 1 mL). The flask was sealed with a teflon screwcap and heated at 90° C. After 2 days, the reaction was cooled to ambient temperature. Purification by preparative HPLC (25 to 100% CH3CN 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 6.3-6.7 min) afforded 2-[4-amino-3-(4-{[(2,3-dichlorophenyl)sulfonyl]amino}-3-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]acetic acid as a white solid (0.006 g, 0.030 mmol): RP-HP (25 to 100% acetonitrile in 0.1 M aqueous ammonium acetate over 10 min at 1 mL/min using a Hypersil HS C18, 250×4.6 mm column) Rt 6.42 min. 1H NMR (DMSO-d6, 400 MHz) δ 8.13 (s, 1H), 7.97 (d, 1H), 7.62 (d, 1H), 7.36 (t, 1H), 7.19 (m, 3H), 7.15 (d, 1H), 4.59 (s, 2H); MS: (M−H)− 509.

Workup

temperaturethe reaction was cooled to ambient temperature
customPurification by preparative HPLC (25 to 100% CH3CN in 0.1 M aqueous ammonium acetate over 20 min at 21 mL/min

Sources & evidence

ORD record: ord-886cb18799334a3a9cb3a7c65b048380
Source dataset: uspto-grants-2003_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06660744B1

Reaction notes

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