1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-(3-fluoro-4-(1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 2241186Notes

Reaction equation

HRID 2241186 reaction equation
COC1C=CC([CH2:7][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](N)=[CH:20][C:19]=4[F:25])=[C:11]3[CH:10]=[N:9]2)=CC=1.CC[N:30]=C=NCCCN(C)C.[F:39][C:40]1[CH:45]=[CH:44][C:43]([NH:46][C:47]([C:49]2([C:52]([OH:54])=O)[CH2:51][CH2:50]2)=[O:48])=[CH:42][CH:41]=1>>[F:25][C:19]1[CH:20]=[C:21]([N:46]([C:43]2[CH:42]=[CH:41][C:40]([F:39])=[CH:45][CH:44]=2)[C:47]([C:49]2([C:52]([NH2:30])=[O:54])[CH2:50][CH2:51]2)=[O:48])[CH:22]=[CH:23][C:18]=1[O:17][C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[N:8]([CH3:7])[N:9]=[CH:10][C:11]=12

Participants

4

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 210815301-[(4-Fluorophenyl)carbamoyl]cyclopropanecarboxylic AcidHCID 685158574-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine

Product 1

HCID 68509792N-(3-fluoro-4-(1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideYield 3%

Procedure

Prepared according to the procedure for Example 2, Step A, substituting 3-fluoro-4-(1-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)benzenamine (22 mg, 0.085 mmol; obtained from Example 3, Step C) for 4-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine. In addition, the amount of EDCI (94 mg, 0.51 mmol) and ((4-fluorophenyl)carbamoyl)cyclopropanecarboxylic acid (117 mg, 0.51 mmol) were both increased. The crude was purified by preparative TLC eluting with EtOAc. The product was obtained as a white solid (1.4 mg, 3%). LRMS (ESI+): 97% purity, 220 nm, m/z 464 (M+1) detected; 1H NMR (400 MHz, CDCl3) δ 10.0 (br s, 1H), 8.35 (d, J=5 Hz, 1H), 8.10 (s, 1H), 7.78 (m, 1H), 7.76 (s, 1H), 7.45 (m, 2H), 7.23 (m, 1H), 7.07 (m, 2H), 6.41 (d, J=5 Hz, 1H), 4.14 (s, 3H), 1.81 (m, 2H), 1.62 (m, 2H).

Workup

  1. customPrepared
  2. customThe crude was purified by preparative TLC
  3. washeluting with EtOAc

Sources & evidence

ORD record
ord-02c9a46b8ab3483f9d9211fd939377de
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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