Hydrochloric Acid → HCID 89691140, compound

HRID 1504052Notes

Reaction equation

HRID 1504052 reaction equation
[C:1]([CH2:4][C@H:5]1[CH2:16][CH2:15][C:14]2[S:13][C:12]3[N:11]=[CH:10][N:9]=[C:8]([O:17][CH:18]4[CH2:23][CH2:22][C:21]([N:25](C)[C:26](=O)OC(C)(C)C)([CH3:24])[CH2:20][CH2:19]4)[C:7]=3[C:6]1=2)(=[O:3])[NH2:2].Cl>ClCCl>[CH3:24][C:21]1([NH:25][CH3:26])[CH2:22][CH2:23][CH:18]([O:17][C:8]2[C:7]3[C:6]4[C@@H:5]([CH2:4][C:1]([NH2:2])=[O:3])[CH2:16][CH2:15][C:14]=4[S:13][C:12]=3[N:11]=[CH:10][N:9]=2)[CH2:19][CH2:20]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86695208HCID 86695208, compound

Product 1

HCID 89691140HCID 89691140, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 50-mL round-bottom flask containing a solution of tert-butyl N-(4-[[(3R)-3-(carbamoylmethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]-1-methylcyclohexyl)-N-methylcarbamate (85 mg, 0.18 mmol, 1.00 equiv) in dichloromethane (5 mL) was added hydrochloric acid (6 M, 0.1 mL) at 0° C. The resulting solution was stirred for 2 h at room temperature and concentrated under vacuum. The crude product (70 mg) was purified by preparative HPLC under the following conditions (Waters): column: XBridge Prep C18 OBD column: 5 um, 19*150 mm; mobile phase: water with 0.05% NH4HCO3 and CH3CN (10% CH3CN up to 30% in 10 min, up to 95% in 2 min, down to 10% in 2 min); flow rate: 20 mL/min; UV detection at 254 & 220 nm. This resulted in 46.9 mg (70%) of 2-[(3R)-12-[[4-methyl-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]acetamide as a white solid. MS: m/z 375 (M+H)+. 1H NMR (300 MHz, CD3OD): δ 8.47 (1H, s), 5.44 (1H, m), 3.84 (1H, m), 3.14 (1H, m), 3.02 (1H, m), 2.79 (1H, m), 2.25-2.35 (5H, m), 2.10 (2H, m), 1.75-1.90 (4H, m), 1.63 (2H, m), 1.19 (3H, s).

Workup

  1. concentrationconcentrated under vacuum
  2. customThe crude product (70 mg) was purified by preparative HPLC under the following conditions (Waters)
  3. waitmobile phase: water with 0.05% NH4HCO3 and CH3CN (10% CH3CN up to 30% in 10 min
  4. waitup to 95% in 2 min
  5. waitdown to 10% in 2 min)
  6. customThis resulted in 46.9 mg (70%) of 2-[(3R)-12-[[4-methyl-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]acetamide as a white solid

Sources & evidence

ORD record
ord-5b9c4e78779545038d3da0e894ce21d3
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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