Diisopropylethylamine → HCID 69432991, compound

HRID 1376052Notes

Reaction equation

HRID 1376052 reaction equation
[CH3:1][O:2][C:3](=[O:21])[NH:4][CH2:5][CH:6]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=1[F:20])[N:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1.[C:22]([O:26][C:27]([N:29]1[CH:38]([C:39](=[O:53])[NH:40][CH:41]([C:50](O)=[O:51])[CH2:42][C:43]2[CH:48]=[CH:47][C:46]([Cl:49])=[CH:45][CH:44]=2)[CH2:37][C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[C:22]([O:26][C:27]([N:29]1[CH:38]([C:39](=[O:53])[NH:40][CH:41]([CH2:42][C:43]2[CH:48]=[CH:47][C:46]([Cl:49])=[CH:45][CH:44]=2)[C:50]([N:10]2[CH2:11][CH2:12][N:7]([CH:6]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=3[F:20])[CH2:5][NH:4][C:3]([O:2][CH3:1])=[O:21])[CH2:8][CH2:9]2)=[O:51])[CH2:37][C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:30]1)=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22083286HCID 22083286, compoundHCID 58786451HCID 58786451, compound

Product 1

HCID 69432991HCID 69432991, compoundYield 98%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To [2-(2,4-Difluoro-phenyl)-2-piperazin-1-yl-ethyl]-carbamic acid methyl ester (516) (0.14 g, 0.47 mmol), 3-[1-Carboxy-2-(4-chloro-phenyl)-ethylcarbamoyl]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (0.22 g, 0.47 mmol) and O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.178 g, 0.47 mmol) was added MeCl2 (1.0 mL) and DMF (0.2 mL) followed by DIPEA (0.82 mL, 4.7 mmol). The reaction was allowed to stir at room temperature for 4 h. The reaction mixture was then concentrated to dryness. The resulting residue was taken up in EtOAc (30 mL) and washed with sat. NaHCO3 (30 mL) and brine (30 mL). The organic phase was concentrated to dryness. The crude material was purified by chromatography (silica gel 60 mesh, eluting with a gradient of 100% EtOAc to 5% TEA/5% MeOH in EtOAc) yielding 0.34 g (98%) pure product.

Workup

  1. concentrationThe reaction mixture was then concentrated to dryness
  2. washwashed with sat. NaHCO3 (30 mL) and brine (30 mL)
  3. concentrationThe organic phase was concentrated to dryness
  4. customThe crude material was purified by chromatography (silica gel 60 mesh
  5. washeluting with a gradient of 100% EtOAc to 5% TEA/5% MeOH in EtOAc)

Sources & evidence

ORD record
ord-483866bb758e404d8b39ca90b5d88bdf
Source dataset
uspto-grants-2007_01
Patent number
US07169777B2

Reaction notes

Loading…