Water → HCID 44544607, compound

HRID 2425792Notes

Reaction equation

HRID 2425792 reaction equation
[C:1]1([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:6]=[CH:5][C:4]([C@@:7]2([S:30][CH3:31])[CH2:11][N:10]([C:12](=[O:26])[C@@H:13]([NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:14]([CH3:17])([CH3:16])[CH3:15])[C@H:9]([C:27]([OH:29])=O)[CH2:8]2)=[CH:3][CH:2]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:49][C@:50]1([C:55]([NH:57][S:58]([CH:61]2[CH2:63][CH2:62]2)(=[O:60])=[O:59])=[O:56])[CH2:52][C@H:51]1[CH:53]=[CH2:54].O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[C:1]1([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:6]=[CH:5][C:4]([C@@:7]2([S:30][CH3:31])[CH2:11][N:10]([C:12](=[O:26])[C@@H:13]([NH:18][C:19](=[O:20])[O:21][C:22]([CH3:25])([CH3:23])[CH3:24])[C:14]([CH3:16])([CH3:17])[CH3:15])[C@H:9]([C:27](=[O:29])[NH:49][C@:50]3([C:55](=[O:56])[NH:57][S:58]([CH:61]4[CH2:63][CH2:62]4)(=[O:60])=[O:59])[CH2:52][C@H:51]3[CH:53]=[CH2:54])[CH2:8]2)=[CH:3][CH:2]=1

Participants

7

Reactant 5

HCID 962WaterHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57998007HCID 57998007, compoundHCID 72163227Cyclopropanecarboxamide, 1-amino-N-(cyclopropylsulfonyl)-2-ethenyl-, (1R,2S)-, 4-methylbenzenesulfonate (1:1)

Product 1

HCID 44544607HCID 44544607, compoundYield 49.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To an iced slurry of (2S,4R)-4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoyl)-4-(methylthio)pyrrolidine-2-carboxylic acid (26 mg, 0.049 mmol), (1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide, p-toluenesulfonate salt, H2O (24.85 mg, 0.059 mmol), and HATU (28.1 mg, 0.074 mmol) in DCM (1 mL) was added N,N-diisopropylethylamine (0.026 mL, 0.148 mmol). The formed colorless slurry was stirred at room temperature overnight (it became light yellow solution). Diluted with DCM, quenched with 5% citric acid. The separated organic layer was washed with sat. sodium citrate and brine, dried over MgSO4, filtered, evaporated in vacuo. The residue was purified by prep-HPLC to afford the desired product tert-butyl (S)-1-((2S,4R)-4-(biphenyl-4-yl)-2-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)-4-(methylthio)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate (18 mg, 0.024 mmol, 49.3% yield) as a white solid. 1H NMR (500 MHz, MeOD) ppm 1.03-1.12 (m, 11H), 1.25 (d, J=3.36 Hz, 2H), 1.43-1.48 (m, 1H), 1.50 (s, 9H), 1.88 (dd, J=8.09, 5.34 Hz, 1H), 1.92 (s, 3H), 2.16-2.27 (m, 1H), 2.38 (t, J=11.29 Hz, 1H), 2.82 (dd, J=11.90, 6.10 Hz, 1H), 2.90-2.99 (m, 1H), 3.97-4.04 (m, 2H), 4.48-4.53 (m, 1H), 5.03 (d, J=10.99 Hz, 1H), 5.13 (d, J=10.68 Hz, 1H), 5.30 (d, J=17.40 Hz, 1H), 5.70-5.81 (m, 1H), 7.37 (t, J=7.02 Hz, 1H), 7.46 (t, J=7.48 Hz, 2H), 7.57-7.64 (m, 4H), 7.64-7.73 (m, 2H). LC-MS (retention time: 3.28 min, method B), MS m/z 739 (M+H).

Workup

  1. customquenched with 5% citric acid
  2. washThe separated organic layer was washed with sat. sodium citrate and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-0b3dd5afccd843c4bf6f791bd5c1cb17
Source dataset
uspto-grants-2011_06
Patent number
US07964560B2

Reaction notes

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