Triethylamine → HCID 66558416, compound

HRID 1530508Notes

Reaction equation

HRID 1530508 reaction equation
[N:1]1([CH2:6][C@@H:7]2[CH2:11][CH2:10][CH2:9][NH:8]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.CCN(CC)CC.[CH:19]([N:22]1[C:26]([C:27]2[N:36]=[C:35]3[N:29]([CH2:30][CH2:31][O:32][C:33]4[CH:40]=[CH:39][C:38]([S:41](Cl)(=[O:43])=[O:42])=[CH:37][C:34]=43)[CH:28]=2)=[N:25][CH:24]=[N:23]1)([CH3:21])[CH3:20]>C(Cl)Cl>[CH:19]([N:22]1[C:26]([C:27]2[N:36]=[C:35]3[C:34]4[CH:37]=[C:38]([S:41]([N:8]5[CH2:9][CH2:10][CH2:11][C@H:7]5[CH2:6][N:1]5[CH2:5][CH2:4][CH2:3][CH2:2]5)(=[O:43])=[O:42])[CH:39]=[CH:40][C:33]=4[O:32][CH2:31][CH2:30][N:29]3[CH:28]=2)=[N:25][CH:24]=[N:23]1)([CH3:21])[CH3:20]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 853152(S)-(+)-1-(2-Pyrrolidinylmethyl)pyrrolidineHCID 86671461HCID 86671461, compound

Product 1

HCID 66558416HCID 66558416, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of (S)-2-pyrrolidin-1-ylmethylpyrrolidine (36 mg, 0.23 mmol) and NEt3 (54 μL, 0.39 mmol) in DCM (5 mL) at 0° C. was added a suspension of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene-9-sulfonyl chloride from Example 121 (64 mg, 0.08 mmol) in DCM (5 mL) and the resulting mixture warmed to RT after 10 min then stirred for 16 h. The reaction mixture was diluted with DCM, washed with a saturated aqueous NaHCO3 solution then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 2-10% 2M NH3/MeOH in DCM then C18, gradient 15-40% MeOH in H2O). The resulting residue was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH affording 123 (22 mg, 56%). LCMS: RT 2.90 min [M+H]+ 512.3. 1H NMR (DMSO, 400 MHz): δ 9.01 (1H, d, J=2.40 Hz), 7.95 (1H, s), 7.82 (1H, s), 7.77 (1H, dd, J=8.65, 2.41 Hz), 7.26 (1H, d, J=8.65 Hz), 5.90-5.89 (1H, m), 4.61-4.60 (4H, m), 3.79-3.69 (1H, m), 3.42-3.41 (1H, m), 3.30-3.24 (1H, m), 2.76 (1H, dd, J=12.12, 4.10 Hz), 2.65-2.62 (5H, m), 1.80-1.79 (7H, m), 1.67-1.54 (1H, m). 1.59 (3H, d, J=6.62 Hz), 1.57 (3H, d, J=6.58 Hz)

Workup

  1. washwashed with a saturated aqueous NaHCO3 solution
  2. dry with materialthen dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 2-10% 2M NH3/MeOH in DCM
  5. washwas washed with MeOH
  6. washthe product eluted with 2M NH3/MeOH affording 123 (22 mg, 56%)

Sources & evidence

ORD record
ord-d938e18c398b45108b65b359a1d13785
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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