Hydrochloric Acid → HCID 86681336, compound

HRID 403341Notes

Reaction equation

HRID 403341 reaction equation
Cl.[Br:2][C:3]1[C:4]([C@@H:9]([NH2:23])[C@H:10]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=2[F:22])[CH2:11][CH2:12][CH:13]=[CH2:14])=[N:5][CH:6]=[CH:7][N:8]=1.[C:24]([O:28][C:29](OC([O-])=O)=[O:30])([CH3:27])([CH3:26])[CH3:25].C(N(CC)CC)C>C(Cl)Cl>[Br:2][C:3]1[C:4]([C@@H:9]([NH:23][C:29](=[O:30])[O:28][C:24]([CH3:27])([CH3:26])[CH3:25])[C@H:10]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=2[F:22])[CH2:11][CH2:12][CH:13]=[CH2:14])=[N:5][CH:6]=[CH:7][N:8]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 22064466Tert-butyldicarbonateHCID 89498927HCID 89498927, compound

Product 1

HCID 86681336HCID 86681336, compoundYield 92.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 250 mL round-bottomed flask was (R)—N-((1S)-1-(3-bromopyrazin-2-yl)-2-(2,3-difluorophenyl)hex-5-enyl)-2-methylpropane-2-sulfinamide (1.96 g, 4.16 mmol) in methanol (17 mL) to give a tan solution. HCl (4M in dioxane, 4.2 mL, 17 mmol) was added, and the mixture was stirred at rt for 1 h. Volatiles were removed in vacuo and the tan residue was diluted with ether and concentrated. The remaining tan foam was directly used in the next reaction. In the same round-bottomed flask was dissolved (1S,2S)-1-(3-bromopyrazin-2-yl)-2-(2,3-difluorophenyl)hex-5-en-1-amine (1.532 g, 4.16 mmol) (crude HCl salt) and t-butylpyrocarbonate (1.449 mL, 6.24 mmol) in methylene chloride (22 mL) to give a tan solution. triethylamine (1.28 mL, 9.15 mmol) was added dropwise, and the mixture was stirred at rt for 2 h. LCMS showed complete conversion. It was concentrated to dryness, and directly subject to flash column chromatography up to 40% ethyl acetate/hexane to afford the desired product (1.80 g, 92% for 2 steps) as colorless oil: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.27 (d, J=17.07 Hz, 2H) 6.92-7.14 (m, 3H) 5.69 (dd, J=10.29, 5.77 Hz, 1H) 5.63 (dd, J=9.41, 5.90 Hz, 1H) 5.41 (d, J=9.54 Hz, 1H) 4.84-4.95 (m, 2H) 3.65 (br. s., 1H) 1.88-2.08 (m, 3H) 1.81 (br. s., 1H) 1.30-1.41 (m, 9H). A slightly more polar diastereomer (generally <10% if there was minimum epimerization at the aldehyde stage) could be removed at this stage: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.46 (d, J=2.26 Hz, 1H) 8.20 (d, J=2.51 Hz, 1H) 6.88-7.11 (m, 3H) 5.66-5.81 (m, 1H) 5.60 (t, J=8.91 Hz, 1H) 5.51 (d, J=9.29 Hz, 1H) 4.83-5.00 (m, 2H) 3.55 (d, Hz, 1H) 1.87-2.06 (m, 3H) 1.73-1.86 (m, 1H) 1.44 (s, 9H).

Workup

  1. customVolatiles were removed in vacuo
  2. additionthe tan residue was diluted with ether
  3. concentrationconcentrated
  4. customThe remaining tan foam was directly used in the next reaction
  5. customto give a tan solution
  6. stirringthe mixture was stirred at rt for 2 h
  7. concentrationIt was concentrated to dryness

Sources & evidence

ORD record
ord-ccbbb7c84f134e94bc8ed0627f8a7cda
Source dataset
uspto-grants-2014_06
Patent number
US08748429B2

Reaction notes

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