Trifluoroacetic acid → 2-(3-fluoro-4-(3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenylamino)-N-(4-fluorophenyl)nicotinamide

HRID 2241397Notes

Reaction equation

COC1C=CC(C[N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH:24][C:25]5[N:40]=[CH:39][CH:38]=[CH:37][C:26]=5[C:27]([NH:29][C:30]5[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=5)=[O:28])=[CH:20][C:19]=4[F:41])=[C:11]3[C:10]([NH:42][CH:43]3[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]3)=[N:9]2)=CC=1.C(O)(C(F)(F)F)=O>>[F:41][C:19]1[CH:20]=[C:21]([NH:24][C:25]2[N:40]=[CH:39][CH:38]=[CH:37][C:26]=2[C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)=[O:28])[CH:22]=[CH:23][C:18]=1[O:17][C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[NH:8][N:9]=[C:10]([NH:42][CH:43]3[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]3)[C:11]=12

Participants

Reactant 2

HCID 6422Trifluoroacetic acid

HCID 685161762-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenylamino)-N-(4-fluorophenyl)nicotinamide

Product 1

HCID 593043722-(3-fluoro-4-(3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenylamino)-N-(4-fluorophenyl)nicotinamideYield 47.4%

Conditions

Temperature: 70 °C

Procedure

A 25 mL round-bottomed flask was charged with 2-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenylamino)-N-(4-fluorophenyl)nicotinamide (0.023 g, 0.0333 mmol) and TFA (3 mL). The reaction mixture was heated to 70° C. for 1 hour. The reaction was concentrated and the residue was purified by preparative TLC [0.5 mm thickness eluting with 15% MeOH(NH3)/CHCl3] to provide the product (9 mg, 46%). LRMS M−1 (571.1) observed. 1H NMR (400 MHz, CDCl3) δ 10.56 (s, 1H), 10.12 (br s, 1H), 8.43 (m, 1H), 8.18 (m, 1H), 8.06 (m, 2H), 7.91 (m, 1H), 7.53 (m, 2H), 7.31 (m, 1H), 7.13 (m, 3H), 6.86 (m, 1H), 6.11 (m, 1H), 4.58 (d, J=7 Hz, 1H), 3.74 (br s, 1H), 2.92 (br s, 2H), 2.37 (s, 3H), 2.27 (br s, 2H), 1.72 (br s, 2H), 1.59 (br s, 1H). 19F NMR (376 MHz, CDCl3) δ −76.0 (3F), −117.0 (1F), −127.6 (1F).

Workup

concentrationThe reaction was concentrated
customthe residue was purified by preparative TLC [0.5 mm thickness eluting with 15% MeOH(NH3)/CHCl3]

Sources & evidence

ORD record: ord-6d5ee81ace704251ab22074f3772211a
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723330B2

Reaction notes

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