Hydrochloric Acid → N-[3-(3-{2-[(7-Amino-5,6,7,8-tetrahydro-2-naphthalenyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]-2-(2-thienyl)acetamide

HRID 1157634Notes

Reaction equation

HRID 1157634 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[CH:19][C:20](C)=[C:21]([NH:23][C:24](=[O:31])[CH2:25][C:26]4[S:27][CH:28]=[CH:29][CH:30]=4)[CH:22]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1.N1([CH2:38][C:39]2[CH:40]=[C:41]([CH:43]=[CH:44][CH:45]=2)[NH2:42])CCCC1.Cl>CC(O)C>[NH2:3][CH:4]1[CH2:38][C:39]2[CH:40]=[C:41]([NH:42][C:2]3[N:7]=[C:6]([C:8]4[C:9]([C:17]5[CH:22]=[C:21]([NH:23][C:24](=[O:31])[CH2:25][C:26]6[S:27][CH:28]=[CH:29][CH:30]=6)[CH:20]=[CH:19][CH:18]=5)=[N:10][N:11]5[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=45)[CH:5]=[CH:4][N:3]=3)[CH:43]=[CH:44][C:45]=2[CH2:6][CH2:5]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 10964073-(Pyrrolidin-1-ylmethyl)anilineHCID 57737250N-{5-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-methylphenyl}-2-(2-thienyl)acetamide

Product 1

HCID 57737171N-[3-(3-{2-[(7-Amino-5,6,7,8-tetrahydro-2-naphthalenyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]-2-(2-thienyl)acetamideYield 44.5%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

N-{5-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-methylphenyl}-2-(2-thienyl)acetamide (100 mg, 0.22 mmol), 3-(1-pyrrolidinylmethyl)aniline (78 mg, 0.44 mmol) and catalytic conc. HCl in iPrOH (4 mL) were heated in a microwave at 180° C. for 10 min. The reaction was concentrated and the residue was dissolved in DCM. The organic solution was washed with saturated NaHCO3 (aq) and water, dried over MgSO4 and concentrated onto silica gel. The crude material was purified by column chromatography. Fractions containing pure product were concentrated, taken up in MeOH and neutralized with MP-carbonate. The mixture was filtered and the filtered concentrated and triturated with DCM and hexanes to give the title compound (28 mg, 21%). 1H NMR (400 MHz, d6-DMSO) δ 9.62 (s, 1H), 9.50 (s, 1H), 8.80 (d, J=6.8 Hz, 1H), 8.50 (d, J=9.2 Hz, 1H), 8.21 (d, J=5.6 Hz, 1H), 7.73 (s, 1H), 7.68 (s, 1H), 7.63 (d, J=8.4 Hz, 1H), 7.45-7.41 (m, 1H), 7.36 (m, 1H), 7.32-7.28 (m, 2H), 7.16 (t, J=7.8 Hz, 1H), 7.11-7.07 (m, 1H), 6.98-6.95 (m, 2H), 6.87 (d, J=7.2 Hz, 1H), 6.50 (d, J=5.6 Hz, 1H), 3.91 (s, 2H), 3.50 (s, 2H), 2.39 (m, 4H), 2.26 (s, 3H), 1.65-1.64 (m, 4H) ppm. ES-LC/MS m/z=600 [M+H]+.

Workup

  1. concentrationThe reaction was concentrated
  2. dissolutionthe residue was dissolved in DCM
  3. washThe organic solution was washed with saturated NaHCO3 (aq) and water
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated onto silica gel
  6. customThe crude material was purified by column chromatography
  7. additionFractions containing pure product
  8. concentrationwere concentrated
  9. filtrationThe mixture was filtered
  10. concentrationthe filtered concentrated
  11. customtriturated with DCM and hexanes

Sources & evidence

ORD record
ord-14a04272c1e2402997f72da2f66f67cc
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

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