Hydrochloric Acid → HCID 86695155, compound

HRID 1503999Notes

Reaction equation

HRID 1503999 reaction equation
[CH2:1]([C:3]1([NH:27]C(=O)OC(C)(C)C)[CH2:8][CH2:7][CH:6]([O:9][C:10]2[C:21]3[C:20]4[C@@H:19]([CH2:22][C@H:23]([OH:26])[CH:24]=[CH2:25])[CH2:18][CH2:17][C:16]=4[S:15][C:14]=3[N:13]=[CH:12][N:11]=2)[CH2:5][CH2:4]1)[CH3:2].Cl>ClCCl>[NH2:27][C:3]1([CH2:1][CH3:2])[CH2:8][CH2:7][CH:6]([O:9][C:10]2[C:21]3[C:20]4[C@@H:19]([CH2:22][C@H:23]([OH:26])[CH:24]=[CH2:25])[CH2:18][CH2:17][C:16]=4[S:15][C:14]=3[N:13]=[CH:12][N:11]=2)[CH2:5][CH2:4]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86695156HCID 86695156, compound

Product 1

HCID 86695155HCID 86695155, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 50-mL round-bottom flask was charged with a solution of tert-butyl N-(1-ethyl-4-[[(3R)-3-[(2S)-2-hydroxybut-3-en-1-yl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)carbamate (35 mg, 0.07 mmol, 1.00 equiv; prepared in a manner analogous to compounds 132.1 and 132.2 in Example 132) and hydrogen chloride (conc.) (0.2 mL) in dichloromethane (10 mL). After stirring for 1 h at 0° C. in an water/ice bath, the reaction was then quenched by the addition of 20 mL of saturated sodium bicarbonate. The resulting solution was extracted with 4×30 mL of ethyl acetate and the organic layers combined and concentrated under vacuum. The crude product (30 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 44.0% in 10 min, up to 95.0% in 2 min, down to 5.0% in 2 min); detector: 254/220 nm. The product was freeze-dried. This resulted in (2S)-1-[(3R)-12-[(4-amino-4-ethylcyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]but-3-en-2-ol (14.6 mg, 52%) as a white solid. 1H NMR (400 MHz, CD3OD): δ: 8.48 (s, 1H), 5.97-5.93 (m, 1H), 5.45-5.43 (m, 1H), 5.29 (d, J=8, 1H), 5.17 (d, J=8, 1H), 4.24-4.26 (m, 1H), 3.39-3.32 (m, 1H), 3.13-2.99 (m 2H), 2.66-2.47 (m, 2H), 2.20-2.16 (m, 3H), 1.93-1.55 (m, 9H), 0.99 (s, 3H). MS: m/z 388 (M+H)+.

Workup

  1. customthe reaction was then quenched by the addition of 20 mL of saturated sodium bicarbonate
  2. extractionThe resulting solution was extracted with 4×30 mL of ethyl acetate
  3. concentrationconcentrated under vacuum
  4. customThe crude product (30 mg) was purified by preparative HPLC under the following conditions (1#-Pre-HPLC-016(Waters))
  5. waitmobile phase: water with 50 mL NH4CO3 and CH3CN (5.0% CH3CN up to 44.0% in 10 min
  6. waitup to 95.0% in 2 min
  7. waitdown to 5.0% in 2 min)
  8. customThe product was freeze-dried
  9. customThis resulted in (2S)-1-[(3R)-12-[(4-amino-4-ethylcyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]but-3-en-2-ol (14.6 mg, 52%) as a white solid

Sources & evidence

ORD record
ord-4bbc4807bb5c4c96bc3663374c7bad2f
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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