1-Hydroxybenzotriazole → HCID 51348851, compound

HRID 2111433Notes

Reaction equation

HRID 2111433 reaction equation
[CH:1]1([N:6]2[C:15]3[N:16]=[C:17]([NH:20][C:21]4[CH:29]=[CH:28][C:24]([C:25]([OH:27])=O)=[CH:23][C:22]=4[O:30][CH3:31])[N:18]=[CH:19][C:14]=3[N:13]([CH3:32])[C:12](=[O:33])[CH:11]3[CH:7]2[CH2:8][CH2:9][CH2:10]3)[CH2:5][CH2:4][CH2:3][CH2:2]1.ON1C2C=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C.[NH2:80][CH:81]1[CH2:86][CH2:85][N:84]([CH3:87])[CH2:83][CH2:82]1>O.CN(C)C=O>[CH:7]1([N:6]2[C:15]3[N:16]=[C:17]([NH:20][C:21]4[CH:29]=[CH:28][C:24]([C:25]([NH:80][CH:81]5[CH2:86][CH2:85][N:84]([CH3:87])[CH2:83][CH2:82]5)=[O:27])=[CH:23][C:22]=4[O:30][CH3:31])[N:18]=[CH:19][C:14]=3[N:13]([CH3:32])[C:12](=[O:33])[CH:2]3[CH:1]2[CH2:5][CH2:4][CH2:3]3)[CH2:11][CH2:10][CH2:9][CH2:8]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27375314-Amino-1-methylpiperidineHCID 66745832HCID 66745832, compound

Product 1

HCID 51348851HCID 51348851, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 0.277 g (0.00061 mole) of (rac)-4-(4-cyclopentyl-9-methyl-10-oxo-1,2,3,3a,4,9,10,10a-octahydro-4,5,7,9-tetraaza-benzo[f]azulen-6-ylamino)-3-methoxy-benzoic acid, 0.129 g (0.00092 mole) of 1-hydroxy-1H-benzotriazole, 0.505 g (0.00092 mole) of benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate, 0.404 g (0.00306 mole) of ethyldiisopropylamine and 40 mL of dimethylformamide was added 0.150 g (0.00092 mole) of 4-amino-1-methyl piperidine. The mixture was stirred overnight at room temperature, then diluted with water and extracted twice with ethyl acetate. The combined ethyl acetate extracts were washed successively with water and then brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (Waters X-terra column), eluting with a gradient of acetonitrile −0.004 M aqueous ammonium acetate to give 0.070 g of (rac)-4-(4-cyclopentyl-9-methyl-10-oxo-1,2,3,3a,4,9,10,10a-octahydro-4,5,7,9-tetraaza-benzo[f]azulen-6-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide (I-68) as a white solid.

Workup

  1. extractionextracted twice with ethyl acetate
  2. washThe combined ethyl acetate extracts were washed successively with water
  3. dry with materialbrine, dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography (Waters X-terra column)
  7. washeluting with a gradient of acetonitrile −0.004 M aqueous ammonium acetate

Sources & evidence

ORD record
ord-ae9e7c269efd419499343b8b465e9808
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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