5-(3-fluoro-4-(1-(4-methoxybenzyl)-3-(4-(morpholine-4-carbonyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one → 5-(3-fluoro-4-(3-(4-(morpholine-4-carbonyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

HRID 2241298Notes

Reaction equation

HRID 2241298 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:41]2[C:42](=[O:55])[N:43]([CH3:54])[C:44]([NH:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[N:45][CH:46]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[N:15](CC3C=CC(OC)=CC=3)[N:16]=[C:17]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[O:25])=[CH:20][CH:19]=3)[C:10]=12>C(O)(C(F)(F)F)=O>[F:1][C:2]1[CH:3]=[C:4]([C:41]2[C:42](=[O:55])[N:43]([CH3:54])[C:44]([NH:47][C:48]3[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=3)=[N:45][CH:46]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[NH:15][N:16]=[C:17]([C:18]3[CH:19]=[CH:20][C:21]([C:24]([N:26]4[CH2:27][CH2:28][O:29][CH2:30][CH2:31]4)=[O:25])=[CH:22][CH:23]=3)[C:10]=12

Participants

3

Reactant 1

HCID 685121275-(3-fluoro-4-(1-(4-methoxybenzyl)-3-(4-(morpholine-4-carbonyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

Product 1

HCID 1359396745-(3-fluoro-4-(3-(4-(morpholine-4-carbonyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-oneYield 59%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 5-(3-fluoro-4-(1-(4-methoxybenzyl)-3-(4-(morpholine-4-carbonyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one (0.014 g, 0.0190 mmol) in TFA (1 mL) was stirred at 60° C. for 3.5 hours. The reaction mixture was concentrated in vacuo to yield a crude yellow gum. The crude product was purified by flash column chromatography, eluting with 10:1 CH2Cl2/MeOH. The isolated product was then partitioned between EtOAc and saturated NaHCO3. The layers were separated and the aqueous layer was re-extracted with EtOAc. The combined EtOAc layers were dried over Na2SO4, filtered and concentrated to yield the desired product (6.9 mg; 59%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.03 (br s, 1H), 8.40 (d, 1H), 8.09 (s, 1H), 8.08 (m, 2H), 7.86 (dd, 1H), 7.66 (m, 1H), 7.57-7.48 (m, 5H), 7.38 (m, 2H), 7.16 (m, 1H), 6.41 (d, 1H), 3.60 (m, 8H), 3.58 (s, 3H). LRMS (APCI pos) m/e 618 (M+1).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customto yield a crude yellow gum
  3. customThe crude product was purified by flash column chromatography
  4. washeluting with 10:1 CH2Cl2/MeOH
  5. customThe isolated product was then partitioned between EtOAc and saturated NaHCO3
  6. customThe layers were separated
  7. extractionthe aqueous layer was re-extracted with EtOAc
  8. dry with materialThe combined EtOAc layers were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-e550c80ce1bb4b91a01479eac1779763
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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