1-Hydroxybenzotriazole → HCID 90220908, compound

HRID 1481907Notes

Reaction equation

HRID 1481907 reaction equation
Cl.[NH2:2][C@@H:3]1[C:9](=[O:10])[N:8]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([Br:22])=[CH:19][CH:20]=3)[CH:15]=[CH:14][C:13]=2[O:23][CH3:24])[C:7]2[CH:25]=[CH:26][C:27]([C:29]#[N:30])=[CH:28][C:6]=2[NH:5][CH2:4]1.[N:31]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])([CH3:37])[C@H:32]([C:34](O)=[O:35])[CH3:33].C1C=CC2N(O)N=NC=2C=1.CCN(C(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.O>[C:41]([O:40][C:38](=[O:39])[N:31]([C@H:32]([C:34](=[O:35])[NH:2][C@@H:3]1[C:9](=[O:10])[N:8]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([Br:22])=[CH:19][CH:20]=3)[CH:15]=[CH:14][C:13]=2[O:23][CH3:24])[C:7]2[CH:25]=[CH:26][C:27]([C:29]#[N:30])=[CH:28][C:6]=2[NH:5][CH2:4]1)[CH3:33])[CH3:37])([CH3:42])([CH3:43])[CH3:44]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 90221221HCID 90221221, compound

Product 1

HCID 90220908HCID 90220908, compoundYield 85.58%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-3-amino-1-(6-bromo-2-methoxy-naphthalen-1-ylmethyl)-2-oxo-2,3,4,5-tetrahydro-1Hbenzo[b][1,4]diazepine-7-carbonitrile hydrochloride (510 mg, 1.047 mmol) in DMF (10 mL) were added Boc-N-Me-Ala-OH (234 mg, 1.15 mmol), HOBT (155.62 mg, 1.15 mmol) and DIPEA (0.943 mL, 5.236 mmol). After 10 min, the mixture was cooled to 0° C. and HBTU (436.7 mg, 1.152 mmol) was added portion wise. The resulting mixture was stirred for 2 h. The mixture was diluted with water and extracted with EtOAc. The extracts were washed with 1 M aqueous citric acid solution, brine, saturated aqueous sodium carbonate solution, dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography to afford the title compound (570 mg, 85.58%) as an off-white solid. LC-MS: 636.0 (M+H).

Workup

  1. extractionextracted with EtOAc
  2. washThe extracts were washed with 1 M aqueous citric acid solution, brine, saturated aqueous sodium carbonate solution
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-f86f64261bf24b38ac1f5f78a4afed37
Source dataset
uspto-grants-2016_08
Patent number
US09409888B2

Reaction notes

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