Hydrochloric Acid → (S)-4-(4-aminophenylthio)-3-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)-N-(4-(2-(1-(2-phenylacetyl)pyrrolidin-2-yl)-1H-imidazol-4-yl)phenyl)benzamide

HRID 44450Notes

Reaction equation

HRID 44450 reaction equation
[CH:1]([C:4]1[CH:5]=[CH:6][C:7]2[C:12]([NH:13][C:14]3[CH:19]=[C:18]([C:20](=[O:47])[NH:21][C:22]4[CH:27]=[CH:26][C:25]([C:28]5[N:29]=[C:30]([C@@H:33]6[CH2:37][CH2:36][CH2:35][N:34]6[C:38](=[O:46])[CH2:39][C:40]6[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=6)[NH:31][CH:32]=5)=[CH:24][CH:23]=4)[CH:17]=[CH:16][C:15]=3[S:48][C:49]3[CH:54]=[CH:53][C:52]([NH:55]C(=O)OC(C)(C)C)=[CH:51][CH:50]=3)=[N:11][CH:10]=[N:9][C:8]=2[N:63]=1)([CH3:3])[CH3:2].Cl.O1CCOCC1>O1CCCC1>[NH2:55][C:52]1[CH:51]=[CH:50][C:49]([S:48][C:15]2[CH:16]=[CH:17][C:18]([C:20]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]4[N:29]=[C:30]([C@@H:33]5[CH2:37][CH2:36][CH2:35][N:34]5[C:38](=[O:46])[CH2:39][C:40]5[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=5)[NH:31][CH:32]=4)=[CH:24][CH:23]=3)=[O:47])=[CH:19][C:14]=2[NH:13][C:12]2[C:7]3[CH:6]=[CH:5][C:4]([CH:1]([CH3:3])[CH3:2])=[N:63][C:8]=3[N:9]=[CH:10][N:11]=2)=[CH:54][CH:53]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 136158805(S)-tert-butyl 4-(2-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)-4-(4-(2-(1-(2-phenylacetyl)pyrrolidin-2-yl)-1H-imidazol-4-yl)phenylcarbamoyl)phenylthio)phenylcarbamate

Product 1

HCID 135890060(S)-4-(4-aminophenylthio)-3-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)-N-(4-(2-(1-(2-phenylacetyl)pyrrolidin-2-yl)-1H-imidazol-4-yl)phenyl)benzamideYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the Product of Example 1K (0.092 g, 0.11 mmol) in tetrahydrofuran (1 mL) was added 4 M HCl in dioxane (1 mL, 4.2 mol) at ambient temperature. After stirred for four hours, the solid HCl salt of the product was filtered off and taken up in a small amount of methanol and added to a NaHCO3 solution. The free amine was extracted into ethyl acetate, concentrated and purified by combi-flash 12 g column, eluting with 0-10% Methanol in dichloromethane to give a yellow solid (0.035 g, 43%). 1H NMR (400 MHz, Solvent) d ppm 1.36 (d, J=7.02 Hz, 6H) 1.89-2.36 (m, 4H) 3.24 (dd, J=13.89, 6.87 Hz, 1H) 3.50-3.81 (m, 4H) 5.09-5.20 (m, 1H) 6.66 (d, J=8.54 Hz, 2H) 6.98-7.10 (m, 2H) 7.12-7.35 (m, 7H) 7.55 (d, J=8.54 Hz, 1H) 7.66-7.79 (m, 5H) 7.96 (s, 1H) 8.49 (s, 1H) 8.76 (d, J=8.24 Hz, 1H)

Workup

  1. filtrationthe solid HCl salt of the product was filtered off
  2. additionadded to a NaHCO3 solution
  3. extractionThe free amine was extracted into ethyl acetate
  4. concentrationconcentrated
  5. custompurified by combi-flash 12 g column
  6. washeluting with 0-10% Methanol in dichloromethane

Sources & evidence

ORD record
ord-0fc37d948d04481e9a877d17ba09ef99
Source dataset
uspto-grants-2013_09
Patent number
US08541424B2

Reaction notes

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