Diisopropylethylamine → HCID 67143669, compound

HRID 574256Notes

Reaction equation

HRID 574256 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[CH2:10][N:11]1[C:16](=[O:17])[C:15]([N:18]2[CH2:23][CH2:22][N:21]([CH2:24][C:25]3[CH:26]=[C:27]([CH:31]=[CH:32][CH:33]=3)[C:28](O)=[O:29])[CH2:20][CH2:19]2)=[C:14]([CH3:34])[N:13]([CH2:35][C:36]2[C:41]([C:42]([F:45])([F:44])[F:43])=[CH:40][CH:39]=[CH:38][C:37]=2[F:46])[C:12]1=[O:47])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl-].[CH2:55]([O:57][C:58](=[O:63])[CH2:59][CH2:60][CH2:61][NH2:62])[CH3:56].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:55]([O:57][C:58](=[O:63])[CH2:59][CH2:60][CH2:61][NH:62][C:28](=[O:29])[C:27]1[CH:31]=[CH:32][CH:33]=[C:25]([CH2:24][N:21]2[CH2:22][CH2:23][N:18]([C:15]3[C:16](=[O:17])[N:11]([CH2:10][C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[C:48]4[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=4)[C:12](=[O:47])[N:13]([CH2:35][C:36]4[C:41]([C:42]([F:44])([F:45])[F:43])=[CH:40][CH:39]=[CH:38][C:37]=4[F:46])[C:14]=3[CH3:34])[CH2:19][CH2:20]2)[CH:26]=1)[CH3:56]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67144594HCID 67144594, compoundHCID 131732844HCID 131732844, compound

Product 1

HCID 67143669HCID 67143669, compoundYield 99.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-{4-[3-((R)-2-tert-butoxycarbonylamino-2-phenyl-ethyl)-1-(2-fluoro-6-trifluoromethyl-benzyl)-6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-piperazin-1-ylmethyl}-benzoic acid (40 mg, 0.0541 mmol) and 4-amino-butyric acid ethyl ester chloride (19 mg, 0.108 mmol) in DMF (0.5 mL) was added N,N-diisopropylethylamine(38 μl, 0.216 mmol), after which HBTU (51 mg, 0.162 mmol) was added to the solution, with stirring. The solution was concentrated at room temperature for 6 hrs, with stirring. The residue was diluted in EtOAc and washed with an aqueous saturated sodium bicarbonate solution, an aqueous saturated ammonium chloride solution, and an aqueous saturated sodium chloride solution in that order. After being separated, the organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified using silica gel chromatography (eluent: dichloromethane/methanol, 30/1) and dried in a vacuum to afford 46 mg of the compound as a yellowish solid (yield 99%). 1H NMR (300 MHz, CDCl3) δ 1.24 (3H, t), 1.34 (9H, s), 1.98 (2H, pentet), 2.31 (2H, m), 2.34 (3H, s), 2.44 (2H, t), 2.53 (2H, m), 2.82 (2H, m), 3.53 (2H, q), 3.64 (4H, m), 4.06 (1H, m), 4.12 (2H, q), 4.24 (1H, t), 5.00 (1H, m), 5.45 (2H, dd), 5.78 (1H, m), 6.30 (0.2H, t), 6.77 (0.8H, t), 7.20-7.41 (8H, m), 7.53 (2H, t), 7.83 (1H, d), 7.71 (1H, d), 7.75 (1H, s)

Workup

  1. concentrationThe solution was concentrated at room temperature for 6 hrs
  2. stirringwith stirring
  3. additionThe residue was diluted in EtOAc
  4. washwashed with an aqueous saturated sodium bicarbonate solution
  5. customAfter being separated
  6. dry with materialthe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified
  10. customdried in a vacuum

Sources & evidence

ORD record
ord-9bf65da6144e4be7ab2d02ba9d52852d
Source dataset
uspto-grants-2015_05
Patent number
US09034850B2

Reaction notes

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