Triethylamine → HCID 67436848, compound

HRID 1968899Notes

Reaction equation

HRID 1968899 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]2[CH2:10][C@H:9]2[C:11]([OH:13])=O)=[N:6][CH:7]=1.[C:14]([O:18][C:19](=[O:41])[NH:20][C@H:21]([CH2:26][NH:27][C:28]1[CH:37]=[CH:36][C:35]2[C:30](=[CH:31][CH:32]=[C:33]([CH:38]3[CH2:40][CH2:39]3)[CH:34]=2)[CH:29]=1)[C@@H:22]([CH3:25])[CH2:23][CH3:24])([CH3:17])([CH3:16])[CH3:15].C(N(CC)CC)C.FC1C=CC([C@@H]2C[C@H]2C(Cl)=O)=NC=1>O=S(Cl)Cl.C(Cl)Cl.O>[C:14]([O:18][C:19](=[O:41])[NH:20][C@H:21]([CH2:26][N:27]([C:28]1[CH:37]=[CH:36][C:35]2[C:30](=[CH:31][CH:32]=[C:33]([CH:38]3[CH2:39][CH2:40]3)[CH:34]=2)[CH:29]=1)[C:11]([C@@H:9]1[CH2:10][C@H:8]1[C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][N:6]=1)=[O:13])[C@@H:22]([CH3:25])[CH2:23][CH3:24])([CH3:16])([CH3:17])[CH3:15]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 67435904HCID 67435904, compoundHCID 67436439HCID 67436439, compoundHCID 86658432HCID 86658432, compound

Product 1

HCID 67436848HCID 67436848, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
65 °C

Procedure

Trans-2-(5-fluoro-pyridin-2-yl)-cyclopropanecarboxylic acid (35 mg, 0.16 mmol) was dissolved in SOCl2 (2 mL) and was heated at 65° C. for 3 hrs. Removal of SOCl2 carefully under pump and dried the residue under high vacuum for 3 hrs. To a solution of {(1S,2S)-1-[(6-cyclopropyl-naphthalen-2-ylamino)-methyl]-2-methyl-butyl}-carbamic acid tert-butyl ester (55 mg, 0.14 mmol) and triethylamine (0.084 mL, 0.6 mmol) in DCM (3 mL) at 0° C. was added freshly made trans-2-(5-fluoro-pyridin-2-yl)-cyclopropanecarbonyl chloride in DCM (2 mL) slowly. The reaction mixture was then stirred at r.t. for 18 hrs. The reaction mixture was transferred to a separatory funnel containing water (20 mL). The aqueous layer was extracted with DCM (3×20 mL). The combined organic layers were washed with brine (20 mL), dried over MgSO4, filtered and concentrated. The residue was purified by Prep HPLC to afford [(1S,2S)-1-({(6-cyclopropyl-naphthalen-2-yl)-[trans-2-(5-fluoro-pyridin-2-yl)-cyclopropanecarbonyl]-amino}-methyl)-2-methyl-butyl]-carbamic acid tert-butyl ester as a solid: LC/MS (ESI) m/e 546 [(M+H)+, calcd for C33H40FN3O3 545.7].

Workup

  1. customRemoval of SOCl2 carefully under pump
  2. customdried the residue under high vacuum for 3 hrs
  3. customThe reaction mixture was transferred to a separatory funnel
  4. extractionThe aqueous layer was extracted with DCM (3×20 mL)
  5. washThe combined organic layers were washed with brine (20 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by Prep HPLC

Sources & evidence

ORD record
ord-6ccc117f17ba42a7828b96177d89bd17
Source dataset
uspto-grants-2013_04
Patent number
US08426414B2

Reaction notes

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