3-Fluorobenzoic Acid → 3-fluoro-N-(6-{[3-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-5-yl]oxy}-1-methyl-1H-indazol-3-yl)benzamide

HRID 1045511Notes

Reaction equation

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

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of 5-[(3-amino-1-methyl-1H-indazol-6-yl)oxy]-3-(4-methoxybenzyl)-3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one (100.00 mg; 0.23 mmol; 1.00 eq.),3-fluorobenzoic acid (35.80 mg; 0.26 mmol; 1.10 eq.), pybop (157.16 mg; 0.30 mmol; 1.30 eq.), DMF (4.00 ml), and N,N-diisopropylethylamine (115.48 μl; 0.70 mmol; 3.00 eq.) was stirred at room temperature for 22 hr. Additional pybop was added and the reaction was heated to 100 degrees C. but the reaction did not go to completion. The reaction was concentrated, redissolved in DMSO, and purified via prep HPLC to afford 17 mg (26%) of 3-fluoro-N-(6-{[3-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-5-yl]oxy}-1-methyl-1H-indazol-3-yl)benzamide as a yellow solid. LC-MS (M+H=553, obsd.=553).

Workup

additionAdditional pybop was added
concentrationThe reaction was concentrated
dissolutionredissolved in DMSO
custompurified via prep HPLC

Sources & evidence

ORD record: ord-12c80b5c4645413b881a02e34ef205a6
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569295B2

Reaction notes

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