Ammonia → HCID 178451172, compound

HRID 424529Notes

Reaction equation

HRID 424529 reaction equation
[N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[N:12]([CH2:13][CH2:14][N:15]3[CH2:19][CH2:18][CH2:17][C@H:16]3[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:11][CH2:10][S:9][C:8]=2[CH:27]=1)([O-])=O.CCO.I.[S:32]1[CH:36]=[CH:35][CH:34]=[C:33]1[C:37](SC)=[NH:38].N>[Pd].CO.C(Cl)Cl>[C:23]([O:22][C:20]([C@@H:16]1[CH2:17][CH2:18][CH2:19][N:15]1[CH2:14][CH2:13][N:12]1[CH2:11][CH2:10][S:9][C:8]2[CH:27]=[C:4]([NH:1][C:37]([C:33]3[S:32][CH:36]=[CH:35][CH:34]=3)=[NH:38])[CH:5]=[CH:6][C:7]1=2)=[O:21])([CH3:26])([CH3:25])[CH3:24]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 702EthanolHCID 59144185(S)-tert-Butyl-1-(2-(7-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)ethyl)pyrrolidine-2-carboxylateHCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide

Product 1

HCID 178451172HCID 178451172, compoundYield 63.1%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

A round bottom flask containing (S)-tert-butyl 1-(2-(7-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)ethyl)pyrrolidine-2-carboxylate (525 mg, 1.334 mmol) was purged with argon. This flask was charged with palladium on activated carbon (10% wt; 142 mg, 0.133 mmol) followed by EtOH (25 mL). The resulting suspension was evacuated using a pump, and hydrogen was let into the system via a balloon. The mixture was stirred under a balloon filled with hydrogen for 2 hours. At this time, the hydrogen balloon was removed, and methyl thiophene-2-carbimidothioate hydroiodide (761 mg, 2.67 mmol) was added to the mixture. The suspension was stirred at room temperature for 17 hours (overnight). At this time, the mixture was filtered through a pad of Celite, and the pad was rinsed with MeOH (20 mL). The filtrate was concentrated, and the residue partitioned between saturated sodium bicarbonate solution (50 mL) and CH2Cl2 (100 mL). The mixture was transferred to a separatory funnel and extracted. After extraction, the organic layer was separated, dried (Na2SO4), filtered, and concentrated to give a dark residue. This residue was subjected to flash chromatography on silica gel using 2:98 MeOH:CH2Cl2 followed by 3.5:96.5 (2M NH3 in MeOH):CH2Cl2 to give a yellow-green residue (398 mg, 63.1%). 1H-NMR (CDCl3) δ 7.39 (dd, J=1.2, 5.1 Hz, 1H), 7.37 (dd, J=1.2, 3.9 Hz, 1H), 7.05 (dd, J=3.6, 4.8 Hz, 1H), 6.73 (brd, J=5.1 Hz, 1H), 6.71 (brs, 1H), 6.65 (dd, J=2.1, 8.7 Hz, 1H), 4.86 (brs, 2H), 3.63-3.60 (m, 2H), 3.44 (t, J=7.5 Hz, 2H), 3.25-3.19 (m, 1H), 3.11 (brdd, J=5.4, 8.4 Hz, 1H), 3.04-2.94 (m, 3H), 2.71-2.59 (m, 1H), 2.45 (brdd, J=7.8, 16.2 Hz, 1H), 2.13-1.99 (m, 1H), 1.97-1.74 (m, 3H), 1.45 (s, 9H); ESI-MS (m/z, %): 473 (MH+, 90), 417 (85), 276 (100); HPLC Purity: 99.6% a/a.

Workup

  1. customwas purged with argon
  2. customThe resulting suspension was evacuated
  3. additionfilled with hydrogen for 2 hours
  4. customAt this time, the hydrogen balloon was removed
  5. stirringThe suspension was stirred at room temperature for 17 hours (overnight)
  6. filtrationAt this time, the mixture was filtered through a pad of Celite
  7. washthe pad was rinsed with MeOH (20 mL)
  8. concentrationThe filtrate was concentrated
  9. customthe residue partitioned between saturated sodium bicarbonate solution (50 mL) and CH2Cl2 (100 mL)
  10. customThe mixture was transferred to a separatory funnel
  11. extractionextracted
  12. extractionAfter extraction
  13. customthe organic layer was separated
  14. dry with materialdried (Na2SO4)
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customto give a dark residue

Sources & evidence

ORD record
ord-bda193e62e864ae9a13d1406d4318cc7
Source dataset
uspto-grants-2012_01
Patent number
US08106043B2

Reaction notes

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