Hydrochloric Acid → HCID 178489400, compound

HRID 1865677Notes

Reaction equation

HRID 1865677 reaction equation
C(OC([N:8]1[CH2:11][CH2:10][CH:9]1[C:12](=[O:50])[NH:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:21]=[C:22]3[C:28]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=4[O:35][CH3:36])=[N:27][N:26](COCC[Si](C)(C)C)[C:23]3=[N:24][CH:25]=2)=[CH:16][C:15]=1[C:45](=[O:49])[N:46]([CH3:48])[CH3:47])=O)(C)(C)C.C1(S)C=CC=CC=1.Cl>C(O)(=O)C>[CH3:48][N:46]([CH3:47])[C:45]([C:15]1[CH:16]=[C:17]([C:20]2[CH:21]=[C:22]3[C:28]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=4[O:35][CH3:36])=[N:27][NH:26][C:23]3=[N:24][CH:25]=2)[CH:18]=[CH:19][C:14]=1[NH:13][C:12]([CH:9]1[CH2:10][CH2:11][NH:8]1)=[O:50])=[O:49]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 7969ThiophenolHCID 68663001HCID 68663001, compound

Product 1

HCID 178489400HCID 178489400, compoundYield 32.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

2-{2-Dimethylcarbamoyl-4-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenylcarbamoyl}-azetidine-1-carboxylic acid tert-butyl ester (149.6 mg, 0.213 mmol) was treated with PS-thiophenol (Argonaut Technologies, Inc., 1.0 eq., 317 mg) and 5% hydrochloric acid in acetic acid (5 mL) for 3.5 h. The mixture was filtered and rinsed with ethyl acetate to remove the acetic acid (the solid product stuck in the resin) and then the product was eluted using methanol. The methanol solution was concentrated in vacuo and then lyophilized from acetonitrile/water to afford azetidine-2-carboxylic acid {2-dimethylcarbamoyl-4-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-amide (32.3 mg, 32.2%). 1H-NMR (500 MHz, dimethylsulfoxide-d6) δ 2.24 (m, 1H), 2.57 (m, 1H), 2.95 (s, 3H), 3.04 (s, 3H), 3.15 (m, 1H), 3.63 (q, J=7.5 Hz, 1H), 3.84 (s, 3H), 4.23 (m, 1H), 7.08 (t, J=7.0 Hz, 1H), 7.21 (d, J=8.5 Hz, 1H), 7.45 (dd, J=2.0, J=7.5 Hz 1H), 7.64 (dd, J=1.5 Hz, J=9.0 Hz, 1H), 8.33 (d, J=8.0 Hz, 1H), 8.35 (s, 1H), 8.87 (d, J=2.5 Hz, 1H), 10.31 (s, 1H). MS: m/z 471 (M+H+).

Workup

  1. filtrationThe mixture was filtered
  2. washrinsed with ethyl acetate
  3. customto remove the acetic acid (the solid product
  4. washwas eluted
  5. concentrationThe methanol solution was concentrated in vacuo

Sources & evidence

ORD record
ord-87c0f975206e4ead96f836bfa417e467
Source dataset
uspto-grants-2009_12
Patent number
US07626021B2

Reaction notes

Loading…