Trifluoroacetic acid → 1-(benzo[d]oxazol-2-yl)-N-(4-(3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)cyclopropanecarboxamide

HRID 2241360Notes

Reaction equation

HRID 2241360 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]([C:27]5([C:30]6[O:31][C:32]7[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=7[N:34]=6)[CH2:29][CH2:28]5)=[O:26])=[CH:20][C:19]=4[F:39])=[C:11]3[C:10]([N:40]3[CH2:45][CH2:44][CH:43]([N:46]([CH3:48])[CH3:47])[CH2:42][CH2:41]3)=[N:9]2)=CC=1.C(O)(C(F)(F)F)=O>>[O:31]1[C:32]2[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=2[N:34]=[C:30]1[C:27]1([C:25]([NH:24][C:21]2[CH:22]=[CH:23][C:18]([O:17][C:16]3[CH:15]=[CH:14][N:13]=[C:12]4[NH:8][N:9]=[C:10]([N:40]5[CH2:41][CH2:42][CH:43]([N:46]([CH3:47])[CH3:48])[CH2:44][CH2:45]5)[C:11]=34)=[C:19]([F:39])[CH:20]=2)=[O:26])[CH2:28][CH2:29]1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 685161541-(benzo[d]oxazol-2-yl)-N-(4-(3-(4-(dimethylamino)piperidin-1-yl)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)cyclopropanecarboxamide

Product 1

HCID 593043211-(benzo[d]oxazol-2-yl)-N-(4-(3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)cyclopropanecarboxamideYield 50%

Conditions

Temperature
50 °C

Procedure

To a flask containing N-(4-(1-(4-methoxybenzyl)-3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-1-(benzo[d]oxazol-2-yl)cyclopropanecarboxamide (6.6 mg, 0.01 mmol) at room temperature under a drying tube was added TFA (2 mL). The reaction was warmed to 50° C. overnight. The reaction was cooled to room temperature and was concentrated. The residue was dissolved in 10 mL dichloromethane and stirred rapidly with 10 mL 10% sodium carbonate solution. The layers were separated and the organics dried (MgSO4). The crude product was concentrated and the crude material was loaded onto a Biotage 12S column with dichloromethane. The column was eluted with a step gradient of dichloromethane (150 mL) and 94.5/5/0.5 dichloromethane/MeOH, concentrated ammonium hydroxide to provide the desires product as a yellow glass (2.7 mg, 50% yield). 1H NMR (400 MHz, CDCl3) δ 12.17 (br s, 1H), 9.92 (br s, 1H), 8.24 (d, 1H), 7.90 (m, 1H), 7.73 (m, 1H), 7.48 (m, 2H), 7.38 (m, 2H), 7.30 (m, 1H), 6.21 (d, 1H), 4.11 (m, 2H), 2.91 (m, 2H), 2.40 (m, 1H), 2.34 (s, 6H), 2.08 (m, 2H), 1.96 (br m, 2H), 1.90 (m, 2H), 1.74 (br m, 2H). LCMS (APCI+): m/z 556 (M+1) detected.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. concentrationwas concentrated
  3. dissolutionThe residue was dissolved in 10 mL dichloromethane
  4. customThe layers were separated
  5. dry with materialthe organics dried (MgSO4)
  6. concentrationThe crude product was concentrated
  7. washThe column was eluted with a step gradient of dichloromethane (150 mL) and 94.5/5/0.5 dichloromethane/MeOH, concentrated ammonium hydroxide

Sources & evidence

ORD record
ord-430fb36ede244a7d9710106c5802ea80
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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