Diisopropylethylamine → (S)-tert-butyl 2-((3aS,4R,6aR)-2-(3-(trifluoromethyl)phenylsulfonyl)octahydrocyclopenta[c]pyrrol-4-ylcarbamoyl)pyrrolidine-1-carboxylate

HRID 2363582Notes

Reaction equation

HRID 2363582 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:40][C:41]([F:61])([F:60])[C:42]1[CH:43]=[C:44]([S:48]([N:51]2[CH2:55][C@H:54]3[C@H:56]([NH2:59])[CH2:57][CH2:58][C@H:53]3[CH2:52]2)(=[O:50])=[O:49])[CH:45]=[CH:46][CH:47]=1.C(N(C(C)C)C(C)C)C>ClCCl>[F:61][C:41]([F:40])([F:60])[C:42]1[CH:43]=[C:44]([S:48]([N:51]2[CH2:55][C@H:54]3[C@H:56]([NH:59][C:13]([C@@H:9]4[CH2:10][CH2:11][CH2:12][N:8]4[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[O:15])[CH2:57][CH2:58][C@H:53]3[CH2:52]2)(=[O:49])=[O:50])[CH:45]=[CH:46][CH:47]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66590613(3aS,4R,6aR)-2-(3-(Trifluoromethyl)phenylsulfonyl)octahydrocyclopenta[c]pyrrol-4-amine

Product 1

HCID 66590188(S)-tert-butyl 2-((3aS,4R,6aR)-2-(3-(trifluoromethyl)phenylsulfonyl)octahydrocyclopenta[c]pyrrol-4-ylcarbamoyl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-1-(tert-Butoxycarbonyl)pyrrolidine-2-carboxylic acid (53.1 mg, 0.247 mmol), and 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (94 mg, 0.247 mmol) were combined in dichloromethane (2 mL). After 10 minutes, (3aS,4R,6aR)-2-(3-(trifluoromethyl)phenylsulfonyl)octahydrocyclopenta[c]pyrrol-4-amine (75 mg, 0.224 mmol) from Step A of Example 254 was added. After stirring for 10 more minutes, N-ethyl-N-isopropylpropan-2-amine (0.098 mL, 0.561 mmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction was quenched with saturated NaHCO3 solution, extracted with 2 mL of dichloromethane, washed with 0.1 N HCl, and concentrated in vacuo. The crude material was purified using a 12 g silica gel cartridge with a gradient of 1-5% methanol (2 N ammonia)/dichloromethane over 20 minutes to give the title compound: 1H NMR (501 MHz, pyridine-d5, temperature 90° C.) δ ppm 8.29-8.30 (bs, 1H), 8.13 (d, J=7.9 Hz, 1H), 7.83 (d, J=7.8 Hz, 1H), 7.66-7.72 (m, 1H), 7.64 (t, J=7.9 Hz, 1H), 4.29-4.32 (m, 1H), 4.06-4.10 (m, 1H), 3.68-3.71 (m, 1H), 3.46-3.51 (m, 1H), 3.34-3.42 (m, 1H), 3.26 (dd, J=9.9, 7.4 Hz, 1H), 3.06-3.17 (m, 2H), 2.55-2.57 (m, 2H), 2.09 (d, J=3.0 Hz, 1H), 1.88-1.98 (m, 3H), 1.80-1.88 (m, 1H), 1.59-1.68 (m, 1H), 1.55 (dd, J=13.2, 8.7 Hz, 1H), 1.50 (s, 9H), 1.25-1.37 (m, 1H); MS (ESI+) m/z 532 (M+H)+.

Workup

  1. additionwas added
  2. customThe reaction was quenched with saturated NaHCO3 solution
  3. extractionextracted with 2 mL of dichloromethane
  4. washwashed with 0.1 N HCl
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified
  7. customover 20 minutes

Sources & evidence

ORD record
ord-ea93ec58f81a49d89bee474371fad283
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

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