HCID 89691337, compound → HCID 89691366, compound

HRID 1503997Notes

Reaction equation

HRID 1503997 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>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

3

Reactant 1

HCID 89691337HCID 89691337, compound

Product 1

HCID 89691366HCID 89691366, compoundYield 44.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of tert-butyl N-(4-[[(3R)-3-[(2R)-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 (200 mg, 0.32 mmol, 1.00 equiv), 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-016(Waters)): column: SunFire Prep C18, 19*150 mm 5 um; mobile phase: water WITH 50 mL NH4CO3 and CH3CN (5.0% CH3CN up to 44.5.0% in 10 min, up to 95.0% in 2 min, down to 5.0% in 2 min); detector: 254/220 nm. 57.4 mg product was obtained. This resulted in 57.4 mg (44%) of (2R)-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), 5.25-5.22 (1H, m), 4.00-4.03 (1H, t), 3.61 (1H, m), 3.07-3.10 (1H, m), 2.94-2.98 (1H, m), 2.52-2.68 (4H, m), 2.18-2.39 (2H, m), 1.64-1.71 (3H, m), 1.26-1.34 (2H, m), 1.08-1.13 (3H, d).

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. customThe crude product (200 mg) was purified by preparative HPLC under the following conditions (1#-Pre-HPLC-016(Waters))
  3. waitmobile phase: water WITH 50 mL NH4CO3 and CH3CN (5.0% CH3CN up to 44.5.0% in 10 min
  4. waitup to 95.0% in 2 min
  5. waitdown to 5.0% in 2 min)

Sources & evidence

ORD record
ord-314b7241d4514863a9899059bc46192e
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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