Hydrochloric Acid → HCID 86695150, compound

HRID 1503996Notes

Reaction equation

HRID 1503996 reaction equation
[Si]([O:8][C@H:9]([C:40](=[O:42])[NH2:41])[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]([CH2:38][CH3:39])C(=O)OC(C)(C)C)[CH2:26][CH2:25]4)[C:13]=3[C:12]1=2)(C(C)(C)C)(C)C.Cl.O.CC#N>ClCCl>[CH2:38]([NH:30][CH:27]1[CH2:28][CH2:29][CH:24]([O:23][C:14]2[C:13]3[C:12]4[C@@H:11]([CH2:10][C@H:9]([OH:8])[C:40]([NH2:41])=[O:42])[CH2:22][CH2:21][C:20]=4[S:19][C:18]=3[N:17]=[CH:16][N:15]=2)[CH2:25][CH2:26]1)[CH3:39]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 6342Acetonitrile2×HCID 86695151HCID 86695151, compound

Product 1

HCID 86695150HCID 86695150, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Into a 50-mL round-bottom flask was placed 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-ethylcarbamate (160 mg, 0.26 mmol, 1.00 equiv) and hydrogen chloride (conc.) (0.3 mL) in dichloromethane (3 mL). The resulting solution was stirred for 1 h at 0° C. The resulting mixture was concentrated under vacuum. The crude product (200 mg) was purified by preparative HPLC under the following conditions (1#-Pre-HPLC-015(Waters)): column: Xbridge Prep C18, 5 um, 19*50 mm; mobile phase: water with 50 mmol NH4HCO3 and CH3CN (10% CH3CN up to 25% in 10 min, up to 95% in 1.5 min, down to 10% in 1.5 min); detector: 254/220 nm. 47.3 mg product was obtained. This resulted in 47.3 mg (45%) of (2S)-3-[(3R)-12-[[4-(ethylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]-2-hydroxypropanamide as a white solid. MS: m/z 405 (M+H)+. 1H NMR (300 MHz, CD3OD): δ 8.474 (1H, s), 5.24-5.26 (1H, m), 4.08-4.12 (1H, d), 3.53 (1H, m), 3.04-3.28 (1H, m), 2.92-2.95 (1H, m), 2.50-2.71 (4H, m), 2.40-2.47 (2H, m), 2.15-2.23 (2H, m), 1.98-2.07 (2H, m), 1.61-1.96 (3H, m), 1.26-1.34 (2H, m).

Workup

  1. customInto a 50-mL round-bottom flask was placed
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. customThe crude product (200 mg) was purified by preparative HPLC under the following conditions (1#-Pre-HPLC-015(Waters))
  4. waitup to 95% in 1.5 min
  5. waitdown to 10% in 1.5 min)

Sources & evidence

ORD record
ord-88eb8291302e4b8c8883cbb0ece360e4
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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