Diisopropylethylamine → HCID 70162399, compound

HRID 1018318Notes

Reaction equation

HRID 1018318 reaction equation
[C:1]12([CH2:11][CH2:12][C:13]3[NH:17][C:16]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=4[F:24])=[N:15][C:14]=3[C:25]([OH:27])=O)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:39]([O:46][C:47](=[O:51])[CH2:48][CH2:49][NH2:50])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1>C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH2:39]([O:46][C:47](=[O:51])[CH2:48][CH2:49][NH:50][C:25]([C:14]1[N:15]=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[F:24])[NH:17][C:13]=1[CH2:12][CH2:11][C:1]12[CH2:2][CH:3]3[CH2:4][CH:5]([CH2:6][CH:7]([CH2:9]3)[CH2:8]1)[CH2:10]2)=[O:27])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 135021004-Methylbenzene-1-sulfonic acid--benzyl beta-alaninate (1/1)HCID 18405648HCID 18405648, compound

Product 1

HCID 70162399HCID 70162399, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 5-(2-adamantan-1-yl-ethyl)-2-(2-fluoro-phenyl)-1H-imidazole-4-carboxylic acid (Example 50) (200 mg, 0.50 mmol) and β-alanine benzyl ester p-toluenesulfonate (175 mg, 0.50 mmol) in DCM (5 ml) was added N,N-diisopropylethylamine (0.26 ml, 1.50 mmol), 4-dimethylaminopyridine (cat.) and bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBrOP) (230 mg, 0.50 mmol). The solution was kept at room temperature for 16 h, diluted with DCM (10 ml), washed with 5% aqueous potassium hydrogen sulphate and with saturated sodium hydrogen carbonate. The organic phase was dried (MgSO4) and the solvent was evaporated. The residue was purified by flash column chromatography (silica, DCM/ethyl acetate 9:1) to afford the product as colourless foam (153 mg, 58%). 1H NMR (300 MHz, CDCl3) 9.72 (1H, br s), 8.23 (1H, m), 7.68 (1H, t), 7.37-7.15 (8H, m), 5.17 (2H, s), 3.73 (2H, m), 3.07 (2H, m), 2.72 (2H, m), 1.97 (3H, s), 1.73-1.41 (14H, m).

Workup

  1. washwashed with 5% aqueous potassium hydrogen sulphate and with saturated sodium hydrogen carbonate
  2. dry with materialThe organic phase was dried (MgSO4)
  3. customthe solvent was evaporated
  4. customThe residue was purified by flash column chromatography (silica, DCM/ethyl acetate 9:1)

Sources & evidence

ORD record
ord-a0f163b25d2c46b5bebdeb40606451de
Source dataset
uspto-grants-2002_11
Patent number
US06479531B1

Reaction notes

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