Hydrochloric Acid → HCID 86345369, compound

HRID 1504092Notes

Reaction equation

HRID 1504092 reaction equation
[Si]([O:8][C@H:9]([C:39](=[O:41])[NH2:40])[CH2:10][C@H:11]1[CH2:22][CH2:21][C:20]2[S:19][C:18]3[N:17]=[CH:16][N:15]=[C:14]([O:23][CH:24]4[CH2:29][CH2:28][CH:27]([N:30](C)[C:31](=O)OC(C)(C)C)[CH2:26][CH2:25]4)[C:13]=3[C:12]1=2)(C(C)(C)C)(C)C.Cl.[NH4+].[OH-]>ClCCl>[OH:8][C@@H:9]([CH2:10][C@H:11]1[CH2:22][CH2:21][C:20]2[S:19][C:18]3[N:17]=[CH:16][N:15]=[C:14]([O:23][CH:24]4[CH2:25][CH2:26][CH:27]([NH:30][CH3:31])[CH2:28][CH2:29]4)[C:13]=3[C:12]1=2)[C:39]([NH2:40])=[O:41]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14923Ammonium HydroxideHCID 86695096HCID 86695096, compound

Product 1

HCID 86345369HCID 86345369, compoundYield 47.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl N-(4-[[(3R)-3-[(2S)-2-[(tert-butyldimethylsilyl)oxy]-2-carbamoylethyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate (160 mg, 0.26 mmol, 1.00 equiv) and hydrogen chloride (conc.) (0.3 mL) in dichloromethane (10 mL) was stirred for 2 h at 0° C. in a water/ice bath. The pH value of the solution was adjusted to 8 with NH4OH. The resulting mixture was concentrated under vacuum. The crude product (150 mg) was purified by preparative HPLC under the following conditions (1#-Pre-HPLC-015(Waters)): Column, Xbridge C18, 19*150 mm, 5 μm; mobile phase: water (50 mM NH4HCO3) and CH3CN (10% CH3CN up to 21% in 15 min, up to 95% in 1.5 min, down to 10% in 1.5 min); UV detection at 254/220 nm. The product was freeze-dried to afford (2S)-2-hydroxy-3-[(3R)-12-[[4-(methylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]propanamide (48.3 mg, 47%) as a white solid. 1H NMR (400 MHz, CD3OD): δ 8.46 (s, 1H), 5.30 (m, 1H), 4.16 (m, 1H), 3.59 (m, 1H), 3.16-2.94 (m, 2H), 2.77-2.68 (m, 1H), 2.58-2.52 (m, 6H), 2.48-2.10 (m, 4H), 1.75-1.72 (m, 3H), 1.66-1.34 (m, 2H). MS: m/z=391 (M+H)+.

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. customThe crude product (150 mg) was purified by preparative HPLC under the following conditions (1#-Pre-HPLC-015(Waters))
  3. waitup to 95% in 1.5 min
  4. waitdown to 10% in 1.5 min)
  5. customThe product was freeze-dried

Sources & evidence

ORD record
ord-1925495db636476bae3716ebfb0ffb07
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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