Hydrochloric Acid → HCID 58660098, compound

HRID 29728Notes

Reaction equation

HRID 29728 reaction equation
Cl.[CH2:2]([O:9][C:10]([NH:12][C@H:13]([C:16]1[CH:21]=[C:20]([CH3:22])[C:19]([CH3:23])=[CH:18][C:17]=1[CH:24]1[CH2:29][CH2:28][N:27]([C:30](OC(C)(C)C)=[O:31])[CH2:26][CH2:25]1)[CH2:14][CH3:15])=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.CCN(C(C)C)C(C)C.Cl.[C:47]([N:51]1[CH2:55][C@@H:54]([C:56]2[CH:61]=[CH:60][C:59]([F:62])=[CH:58][C:57]=2[F:63])[C@H:53](C(O)=O)[CH2:52]1)([CH3:50])([CH3:49])[CH3:48].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CCOC(C)=O.C(Cl)Cl.O>[C:47]([N:51]1[CH2:55][C@@H:54]([C:56]2[CH:61]=[CH:60][C:59]([F:62])=[CH:58][C:57]=2[F:63])[C@H:53]([C:30]([N:27]2[CH2:28][CH2:29][CH:24]([C:17]3[CH:18]=[C:19]([CH3:23])[C:20]([CH3:22])=[CH:21][C:16]=3[C@@H:13]([NH:12][C:10](=[O:11])[O:9][CH2:2][C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH2:14][CH3:15])[CH2:25][CH2:26]2)=[O:31])[CH2:52]1)([CH3:50])([CH3:48])[CH3:49]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58660104tert-butyl 4-[2-((1S)-1-{[(benzyloxy)carbonyl]amino}propyl)-4,5-dimethylphenyl]piperidine-1-carboxylateHCID 67212109(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid hydrochloride

Product 1

HCID 58660098HCID 58660098, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A saturated solution of hydrogen chloride in EtOAc (10.0 mL) was added to a solution of 111 (830 mg, 1.7 mmol) in DCM (5.0 mL) at ambient temperature. After 30 min the volatiles were evaporated in vacuo. The above residue was resuspended in DCM (10.0 mL) and to this stirred solution was added DIEA (886 μL, 5.1 mmol), (3S,4R)-1-tert-butyl4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid 80 (542 mg, 1.7 mmol), and HATU (710 mg, 1.87 mmol). After approximately 18 h, the reaction mixture was poured into water and extracted three times with DCM. The combined organic extracts were washed with brine, dried (MgSO4), filtered, and the filtrate concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (gradient elution; 0%-10% methanol [containing 10% v/v ammonium hydroxide]/DCM as eluent) afforded 112 as a colorless oil.

Workup

  1. customAfter 30 min the volatiles were evaporated in vacuo
  2. extractionextracted three times with DCM
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated in vacuo
  7. customPurification of the crude residue by flash chromatography on silica gel (
  8. washgradient elution
  9. addition0%-10% methanol [containing 10% v/v ammonium hydroxide]/DCM as eluent)

Sources & evidence

ORD record
ord-02855ada0c0c449999ade049b28a8b02
Source dataset
uspto-grants-2008_09
Patent number
US07419990B2

Reaction notes

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