Hydrochloric Acid → HCID 86695173, compound

HRID 1504019Notes

Reaction equation

HRID 1504019 reaction equation
[C:1]([CH2:4][C@@H:5]1[CH2:17][C:16]2[C:15]3[C:14]([O:18][CH:19]4[CH2:24][CH2:23][CH:22]([NH:25]C(=O)OC(C)(C)C)[CH2:21][CH2:20]4)=[N:13][CH:12]=[N:11][C:10]=3[S:9][C:8]=2[CH2:7][CH2:6]1)(=[O:3])[NH2:2].[ClH:33]>ClCCl>[ClH:33].[NH2:25][CH:22]1[CH2:23][CH2:24][CH:19]([O:18][C:14]2[C:15]3[C:16]4[CH2:17][C@@H:5]([CH2:4][C:1]([NH2:2])=[O:3])[CH2:6][CH2:7][C:8]=4[S:9][C:10]=3[N:11]=[CH:12][N:13]=2)[CH2:20][CH2:21]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86695172HCID 86695172, compound

Product 1

HCID 86695173HCID 86695173, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed tert-butyl N-(4-[[(12S)-12-(carbamoylmethyl)-8-thia-4,6-diazatricyclo[7.4.0.0[2,7]]trideca-1(9),2(7),3,5-tetraen-3-yl]oxy]cyclohexyl)carbamate (80 mg, 0.17 mmol, 1.00 equiv) in dichloromethane (5 mL) at 0° C. Then hydrochloric acid (6 M, 0.5 mL) was added and the resulting solution was stirred overnight at room temperature. The resulting mixture was concentrated under vacuum to give 86 mg (crude) of 2-[(12S)-3-[(4-aminocyclohexyl)oxy]-8-thia-4,6-diazatricyclo[7.4.0.0[2,7]]trideca-1(9),2(7),3,5-tetraen-12-yl]acetamide hydrochloride as a yellow solid. The crude hydrochloride dissolved in 5 mL of methanol was added HCHO (37%, 1 mL) and AcOH (0.5 mL). After stirring for 30 min, NaCNBH3 (34 mg, 0.54 mmol, 2.50 equiv) was added and the resulting mixture was stirred overnight at room temperature. The resulting mixture was concentrated under vacuum. The crude product (80 mg) was purified by preparative HPLC under the following conditions (Waters): column: X bridge Prep C18 5 um, 19*150 mm; mobile phase: water with 0.05% NH4HCO3 and CH3CN (5.0% CH3CN up to 41.0% in 9 min, up to 95.0% in 2 min, down to 5.0% in 2 min); flow rate: 20 mL/min; UV detection at 220/254 nm. This resulted in 21.5 mg (26%) of 2-[(12S)-3-[[4-(dimethylamino)cyclohexyl]oxy]-8-thia-4,6-diazatricyclo[7.4.0.0[2,7]]trideca-1(9),2(7),3,5-tetraen-12-yl]acetamide as a white solid. MS: m/z 389 (M+H)+. 1H NMR (400 MHz, CDCl3): δ 8.51 (s, 1H), 5.47-5.40 (d, 2H), 5.25-5.19 (m, 1H), 3.31-3.25 (m, 1H), 2.92-2.90 (m, 2H), 2.61-2.55 (m, 1H), 2.41-2.29 (m, 11H), 2.20-2.15 (m, 1H), 2.13-2.00 (m, 2H), 1.69-1.56 (m, 6H).

Workup

  1. customInto a 50-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. customat 0° C
  4. concentrationThe resulting mixture was concentrated under vacuum

Sources & evidence

ORD record
ord-093c799c28114c27942817f5bb9ebf9c
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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