Hydrochloric Acid → HCID 178489400, compound

HRID 2389014Notes

Reaction equation

HRID 2389014 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-4702ea2bf4974e4aab22b73d9c675a41
Source dataset
uspto-grants-2012_09
Patent number
US08268994B2

Reaction notes

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