Hydrochloric Acid → HCID 23653971, compound

HRID 2109705Notes

Reaction equation

HRID 2109705 reaction equation
[CH3:1][O:2][CH2:3][C:4]1[N:5]=[C:6]([N:18]([CH2:22][C@@H:23]([NH:35][CH2:36][CH2:37][N:38]2[CH2:43][CH2:42][O:41][CH2:40][CH2:39]2)[CH2:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=2)C(=O)C)[S:7][C:8]=1[C:9]1[S:10][C:11]2[CH:12]=[N:13][CH:14]=[CH:15][C:16]=2[N:17]=1.C1COCC1.Cl.[OH-].[Na+]>C(Cl)Cl.CO>[CH3:1][O:2][CH2:3][C:4]1[N:5]=[C:6]([NH:18][CH2:22][C@@H:23]([NH:35][CH2:36][CH2:37][N:38]2[CH2:39][CH2:40][O:41][CH2:42][CH2:43]2)[CH2:24][C:25]2[CH:26]=[CH:27][C:28]([C:31]([F:33])([F:32])[F:34])=[CH:29][CH:30]=2)[S:7][C:8]=1[C:9]1[S:10][C:11]2[CH:12]=[N:13][CH:14]=[CH:15][C:16]=2[N:17]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 23653970HCID 23653970, compound

Product 1

HCID 23653971HCID 23653971, compoundYield 8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

A glass microwave reaction vessel was charged with N-(4-(methoxymethyl)-5-(thiazolo[5,4-c]pyridin-2-yl)thiazol-2-yl)-N-((S)-2-(2-morpholinoethylamino)-3-(4-(trifluoromethyl)phenyl)propyl)acetamide (0.111 g, 0.2 mmol), THF (2.0 mL, 24 mmol), and HCl (2.0 mL, 10 mmol). The reaction mixture was stirred and heated in a Smith Synthesizer® microwave reactor (Personal Chemistry, Inc., Upssala, Sweden) at 150° C. for 12 minutes. The mixture was then made basic with NaOH, extracted with EtOAc, and the organics were adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (4 g), eluting with a gradient of 1% to 10% 2 M NH3.MeOH in DCM, to provide the title compound, 4-(methoxymethyl)-N-((S)-2-(2-morpholinoethylamino)-3-(4-(trifluoromethyl)phenyl)propyl)-5-(thiazolo[5,4-c]pyridin-2-yl)thiazol-2-amine (0.008 g, 8% yield). LCMS (M+H) 593.2 calc. for C27H32F3N6O2S2 593.20. 1H NMR (400 MHz, CD3OD): δ ppm 9.13 (s, 1H), 8.50 (d, J=5.7 Hz, 1H), 7.83 (d, J=5.7 Hz, 1H), 7.62 (d, J=8.1 Hz, 1H), 7.48 (d, J=8.1 Hz, 1H), 4.69 (s, 2H), 3.50 (s, 3H), 3.47 (m, 6H), 3.14 (m, 1H), 2.95 (dd, J=6.0, 13.6 Hz, 1H), 2.84 (dd, J=7.9, 13.6 Hz, 1H), 2.77 (dd, J=5.8, 11.9 Hz, 1H), 2.68 (m, 1H), 2.40 (m, 2H), 2.29 (s, 4H).

Workup

  1. customA glass microwave reaction vessel
  2. extractionextracted with EtOAc
  3. customchromatographed through a Redi-Sep® pre-packed silica gel column (4 g)
  4. washeluting with a gradient of 1% to 10% 2 M NH3

Sources & evidence

ORD record
ord-854b65a6dbc4477188ff04418fd7ce1a
Source dataset
uspto-grants-2009_04
Patent number
US07514566B2

Reaction notes

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