Diisopropylethylamine → HCID 70645119, compound

HRID 473973Notes

Reaction equation

HRID 473973 reaction equation
C(N(C(C)C)C(C)C)C.[CH3:10][C:11]([CH3:43])([CH2:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:32]=[C:31]3[C:26]([C:27]([C:34](=[O:42])[NH:35][C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)=[CH:28][C:29]([CH3:33])=[N:30]3)=[CH:25][CH:24]=2)=[CH:19][N:18]=1)[C:12](O)=[O:13].Br.[N:45]1[NH:46][N:47]=[N:48][C:49]=1[CH2:50][NH2:51].F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>CN(C)C=O>[N:45]1[NH:46][N:47]=[N:48][C:49]=1[CH2:50][NH:51][C:12](=[O:13])[C:11]([CH3:10])([CH3:43])[CH2:15][O:16][C:17]1[N:18]=[CH:19][C:20]([C:23]2[CH:32]=[C:31]3[C:26]([C:27]([C:34]([NH:35][C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=4)=[O:42])=[CH:28][C:29]([CH3:33])=[N:30]3)=[CH:25][CH:24]=2)=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 46926794HCID 46926794, compoundHCID 53444401HCID 53444401, compound

Product 1

HCID 70645119HCID 70645119, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-Ethyl-N,N-diisopropylamine (50.0 μL, 0.300 mmol) was added at room temperature to a solution of 2,2-dimethyl-3-(5-(2-methyl-4-(phenylcarbamoyl)quinolin-7-yl)pyridin-2-yloxy)propanoic acid B-17 (45.5 mg, 0.10 mmol), (2H-tetrazol-5-yl)methanamine hydrobromide (27.7 mg, 0.154 mmol) and (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (64.0 mg, 0.123 mmol) in anhydrous N,N-dimethylformamide (5.0 mL) under an atmosphere of nitrogen. The reaction mixture was stirred overnight, then partitioned between methylene chloride (30 mL) and an aqueous solution of pH 7 phosphate buffer (30 mL). The aqueous layer was extracted with methylene chloride (3×30 mL); the combined extracts were successively washed with water (30 mL), brine (30 mL), then dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure. The crude residue was purified by flash column chromatography on silica gel (hexanes:ethyl acetate gradient) to give 7-(6-(3-((2H-tetrazol-5-yl)methylamino)-2,2-dimethyl-3-oxopropoxy)pyridin-3-yl)-2-methyl-N-phenylquinoline-4-carboxamide B-24 (34.9 mg, Yield=65%). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 6H), 2.77 (s, 3H), 3.71-3.74 (m, 2H), 4.75 (d, J=5.5 Hz, 2H), 6.86 (d, J=8.5 Hz, 1H), 7.23-7.30 (m, 2H), 7.45 (t, J=6.5 Hz, 3H), 7.87 (d, J=8.0 Hz, 2H), 7.87 (d, J=8.5 Hz, 1H), 8.24 (d, J=8.5 Hz, 1H), 8.47 (s, 1H), 8.45 (d, J=9.5 Hz, 1H), 8.59 (s, 1H); MS (ESI) [M+1]+ 537.

Workup

  1. custompartitioned between methylene chloride (30 mL)
  2. extractionThe aqueous layer was extracted with methylene chloride (3×30 mL)
  3. washthe combined extracts were successively washed with water (30 mL), brine (30 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure
  7. customThe crude residue was purified by flash column chromatography on silica gel (hexanes:ethyl acetate gradient)

Sources & evidence

ORD record
ord-0674a8d3f1d240d482bbcbaa4bff8ac5
Source dataset
uspto-grants-2014_01
Patent number
US08637507B2

Reaction notes

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