Hydrochloric Acid → HCID 86695256, compound

HRID 1504093Notes

Reaction equation

HRID 1504093 reaction equation
C(O[C:6]([N:8](C)[CH:9]1[CH2:14][CH2:13][CH:12]([O:15][C:16]2[C:27]3[C:26]4[C@@H:25]([CH2:28][C@H:29]([NH:33]C(=O)OCC5C=CC=CC=5)[C:30](=[O:32])[NH2:31])[CH2:24][CH2:23][C:22]=4[S:21][C:20]=3[N:19]=[CH:18][N:17]=2)[CH2:11][CH2:10]1)=O)(C)(C)C.Cl>ClCCl>[NH2:33][C@@H:29]([CH2:28][C@H:25]1[CH2:24][CH2:23][C:22]2[S:21][C:20]3[N:19]=[CH:18][N:17]=[C:16]([O:15][CH:12]4[CH2:11][CH2:10][CH:9]([NH:8][CH3:6])[CH2:14][CH2:13]4)[C:27]=3[C:26]1=2)[C:30]([NH2:31])=[O:32]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86695217HCID 86695217, compound

Product 1

HCID 86695256HCID 86695256, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
30 °C

Procedure

To a solution of benzyl N-[(1S)-2-[(3R)-12-[(4-[[(tert-butoxy)carbonyl](methyl)amino]cyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]-1-carbamoylethyl]carbamate (70 mg, 0.11 mmol, 1.00 equiv) in dichloromethane (5 mL) was added hydrogen chloride (12 M, 2 mL). The resulting solution was stirred for 5 h at 30° C. and then concentrated under vacuum. The crude product (70 mg) was purified by preparative HPLC under the following conditions: Column: SunFire Prep C18, 19*150 mm, 5 μm; mobile phase: water (with 50 mL NH4HCO3) and CH3CN (5.0% CH3CN up to 43.0% in 12 min, up to 95.0% in 2 min, down to 5.0% in 2 min); UV detection at 254/220 nm. This resulted in 28 mg (64%) of (2S)-2-amino-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 as a white solid. MS (ES): m/z 390 (M+H)+. 1H NMR (300 MHz, CD3OD): δ 1.39-1.55 (m, 3H), 1.72-1.85 (m, 2H), 2.17-2.28 (m, 3H), 2.29-2.39 (m, 3H), 2.56 (s, 3H), 2.63-2.72 (m, 1H), 2.81-3.97 (m, 2H), 3.05-3.15 (m, 1H), 3.35-3.45 (m, 2H), 5.20-5.35 (m, 1H), 8.42 (s, 1H).

Workup

  1. concentrationconcentrated under vacuum
  2. customThe crude product (70 mg) was purified by preparative HPLC under the following conditions
  3. waitmobile phase: water (with 50 mL NH4HCO3) and CH3CN (5.0% CH3CN up to 43.0% in 12 min
  4. waitup to 95.0% in 2 min
  5. waitdown to 5.0% in 2 min)
  6. customThis resulted in 28 mg (64%) of (2S)-2-amino-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 as a white solid

Sources & evidence

ORD record
ord-bba6976041124f298be81a8c618c3f7f
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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