Diisopropylethylamine → HCID 68283882, compound

HRID 1527419Notes

Reaction equation

HRID 1527419 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([F:13])[C@@H:10]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[C@H:9]1[C:22]([OH:24])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:25][C:26]1[C:27]([F:36])=[C:28]([C:32]2([NH2:35])[CH2:34][CH2:33]2)[CH:29]=[CH:30][CH:31]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([F:13])[C@@H:10]([O:14][Si:15]([C:18]([CH3:19])([CH3:20])[CH3:21])([CH3:16])[CH3:17])[C@H:9]1[C:22](=[O:24])[NH:35][C:32]1([C:28]2[CH:29]=[CH:30][CH:31]=[C:26]([Cl:25])[C:27]=2[F:36])[CH2:33][CH2:34]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 55264236HCID 55264236, compoundHCID 68283966HCID 68283966, compound

Product 1

HCID 68283882HCID 68283882, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of (2S,3S,4S)-3-(tert-butyl-dimethyl-silanyloxy)-4-fluoro-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (300 mg, 0.825 mmol), 1-(3-chloro-2-fluoro-phenyl)-cyclopropylamine (prepared as described in Part C, 272 mg, 0.908 mmol) and HBTU (376 mg, 0.99 mmol) in DMF (10 mL) was added DIPEA (0.432 ml, 2.476 mmol) under nitrogen atmosphere. The reaction mixture was stirred 2 h at 25° C. Then quenched by addition of a saturated aqueous solution of NaHCO3 and extracted with EtOAc (×2). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc 1:1). MS (UPLC): 531.5/533.5 [M+H]+, 505.5 [M+NH4]+, 510.4 [M+Na]+; tR (UPLC conditions m): 1.55 min.

Workup

  1. customThen quenched by addition of a saturated aqueous solution of NaHCO3
  2. extractionextracted with EtOAc (×2)
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc 1:1)
  7. custom1.55 min.

Sources & evidence

ORD record
ord-02f9af78242f464c94afd7f203dc8fed
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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