Boron Trichloride → HCID 86718903, compound

HRID 528880Notes

Reaction equation

HRID 528880 reaction equation
C([O:8][CH2:9][CH2:10][O:11][CH2:12][C@@H:13]1[CH2:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][N:14]1[C:23]([C:25]1[CH:30]=[C:29]([C:31](=[O:46])[NH:32][S:33]([C:36]2[CH:45]=[CH:44][C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH:37]=2)(=[O:35])=[O:34])[CH:28]=[CH:27][C:26]=1[N:47]1[C:51]([CH3:52])=[C:50]([Cl:53])[C:49]([C:54]([N:56]([CH2:61][CH2:62][CH2:63][CH3:64])[CH2:57][CH2:58][CH2:59][CH3:60])=[O:55])=[N:48]1)=[O:24])C1C=CC=CC=1.B(Cl)(Cl)Cl>C(Cl)Cl>[CH2:61]([N:56]([CH2:57][CH2:58][CH2:59][CH3:60])[C:54]([C:49]1[C:50]([Cl:53])=[C:51]([CH3:52])[N:47]([C:26]2[CH:27]=[CH:28][C:29]([C:31](=[O:46])[NH:32][S:33]([C:36]3[CH:45]=[CH:44][C:43]4[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=4)[CH:37]=3)(=[O:34])=[O:35])=[CH:30][C:25]=2[C:23]([N:14]2[C@H:13]([CH2:12][O:11][CH2:10][CH2:9][OH:8])[CH2:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15]2)=[O:24])[N:48]=1)=[O:55])[CH2:62][CH2:63][CH3:64]

Participants

4

Reactant 2

HCID 25135Boron Trichloride2×HCID 86718904HCID 86718904, compound

Product 1

HCID 86718903HCID 86718903, compoundYield 31.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of (S)-1-(2-(3-((2-(benzyloxy)ethoxy)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (Example 117, 35 mg, 0.039 mmol) in CH2Cl2 (1.0 mL) was cooled to −78° C., and boron trichloride (270 μL, 0.27 mmol) was added dropwise via syringe. The resulting solution was stirred at −78° C. for 1 h and then at room temperature overnight. Additional boron trichloride (270 μL, 0.27 mmol) was added, and the reaction mixture was stirred at room temperature for 5 h. After quenching with sat. aq. NH4Cl, the solution was extracted with EtOAc (3×). The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was purified by preparative HPLC to give the title compound (10 mg, 31%). 1H NMR (1:1 CD3OD:CDCl3, mixture of amide rotamers) δ 8.65 (s, 1H), 8.40 (s, 0.5H), 8.19-8.11 (m, 1H), 8.09-7.83 (m, 4H), 7.63-7.52 (m, 2.5H), 7.47-7.30 (m, 1H), 7.26-6.98 (m, 3.5H), 6.88 (br s, 0.5H), 5.25 (d, J=18.3 Hz, 0.5H), 4.36-4.07 (m, 3H), 3.75-3.17 (m, 6.5H), 3.12-2.61 (m, 4H), 2.51 (d, J=16.4 Hz, 0.5H), 2.35-2.17 (m, 3.5H), 1.68-0.79 (m, 11.5H), 0.75-0.56 (m, 2.5H); MS(ESI+) m/z 814.2 (M+H)+.

Workup

  1. customat room temperature
  2. customovernight
  3. stirringthe reaction mixture was stirred at room temperature for 5 h
  4. customAfter quenching with sat. aq. NH4Cl
  5. extractionthe solution was extracted with EtOAc (3×)
  6. dry with materialThe combined organic extracts were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-f3617739b9a1426f9db4a2aea1285cac
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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