Ammonia → HCID 178480323, compound

HRID 552972Notes

Reaction equation

HRID 552972 reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[CH2:7][CH2:8][C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([NH2:18])[CH:16]=2)[NH:11][CH:10]=1.I.CS[C:22]([C:24]1[S:25][CH:26]=[CH:27][CH:28]=1)=[NH:23].N.[ClH:30]>CO.CCOCC.C(O)C>[ClH:30].[ClH:30].[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[CH2:7][CH2:8][C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([NH:18][C:22]([C:24]3[S:25][CH:26]=[CH:27][CH:28]=3)=[NH:23])[CH:16]=2)[NH:11][CH:10]=1

Participants

8

Reactant 4

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 59715802(R)-3-(2-(1-methylpyrrolidin-2-yl)ethyl)-1H-indol-5-amineHCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide

Product 1

HCID 178480323HCID 178480323, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolvent2×HCID 3283Diethyl EtherSolvent2×

Procedure

To an argon purged round bottom flask was charged 146 (40 mg, 0.164 mmol) and thiophene-2-carboximidothioic acid methyl ester hydroiodide (94 mg, 0.329 mmol) followed by absolute ethanol (3 mL). The reaction was stirred using a magnetic stirbar for 60 hours at room temperature. TLC (10% 2 M ammonia in methanol/90% dichloromethane) revealed all starting amine had reacted. The reaction as treated with ether (50 mL). The resulting yellow precipitate was collected by vacuum filtration and washed with ether. The precipitate was washed from the filter using methanol. The residue was concentrated, and purified by silica gel column chromatography (5-10% 2M ammonia in methanol/95-90% dichloromethane) to afford a yellow oil. The purified product was dissolved in anhydrous methanol (3 mL) and treated with 1M hydrogen chloride in ether (5 mL). After stirring for 30 minutes the precipitate was collected by vacuum filtration. The precipitate was washed with ether, followed by washing from the filter with methanol. The filtrate was concentrated and dried under high vacuum. Yield: 21 mg of yellow solid, compound 147 (30%) Melting point 212° C. 1H NMR (MeOD-d3) δ 8.09 (br s, 2H), 7.76 (s, 1H), 7.59 (d, 1H, J=8.7 Hz), 7.41 (br s, 1H), 7.35 (s, 1H), 7.19 (d, 1H, J=8.7 Hz), 3.67 (br m, 1H), 3.19 (br m, 1H), 3.1-2.8 (br m, 2H), 2.91 (s, 3H), 2.46 (br m, 2H), 2.2-1.8 (br m, 5H). MS (TOF+): Exact calc. for C20H25N4S 353.1794 (MH+), found 353.1782.

Workup

  1. customfor 60 hours
  2. customat room temperature
  3. customhad reacted
  4. customThe reaction
  5. filtrationThe resulting yellow precipitate was collected by vacuum filtration
  6. washwashed with ether
  7. washThe precipitate was washed from the filter
  8. concentrationThe residue was concentrated
  9. custompurified by silica gel column chromatography (5-10% 2M ammonia in methanol/95-90% dichloromethane)
  10. customto afford a yellow oil
  11. stirringAfter stirring for 30 minutes the precipitate
  12. filtrationwas collected by vacuum filtration
  13. washThe precipitate was washed with ether
  14. washby washing from the
  15. filtrationfilter with methanol
  16. concentrationThe filtrate was concentrated
  17. customdried under high vacuum

Sources & evidence

ORD record
ord-e9d9f5f435684fdfb474edd782c21b56
Source dataset
uspto-grants-2011_05
Patent number
US07951940B2

Reaction notes

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