Hydrochloric Acid → HCID 57639182, compound

HRID 2111597Notes

Reaction equation

HRID 2111597 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:30](=[O:38])[NH:31][S:32]([N:35]([CH3:37])[CH3:36])(=[O:34])=[O:33])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]([OH:23])=O)=[CH:18][C:17]4[CH:24]=[C:25]([O:28][CH3:29])[CH:26]=[CH:27][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.Cl.C([N:48]1[CH2:56][C@H:55]2[C@H:50]([NH:51][CH2:52][CH2:53][CH2:54]2)[CH2:49]1)C1C=CC=CC=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl>CN(C=O)C.[Pd].CO.CCOC(C)=O.O>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:30]([NH:31][S:32]([N:35]([CH3:36])[CH3:37])(=[O:33])=[O:34])=[O:38])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]([N:51]4[CH2:52][CH2:53][CH2:54][C@H:55]5[CH2:56][NH:48][CH2:49][C@@H:50]45)=[O:23])=[CH:18][C:17]4[CH:24]=[C:25]([O:28][CH3:29])[CH:26]=[CH:27][C:16]=4[C:15]=23)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 448909431059609-67-4HCID 59682115HCID 59682115, compound

Product 1

HCID 57639182HCID 57639182, compoundYield 61%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

To a solution of 13-cyclohexyl-10-(((dimethylamino)sulfonyl)carbamoyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6-carboxylic acid (178 mg, 0.33 mmol) and (4aS,7aS)-6-benzyloctahydro-1H-pyrrolo[3,4-b]pyridine dihydrochloride (114 mg, 0.40 mmol) in DMF (3 mL) and TEA (0.2 mL) was added HATU (162 mg, 0.43 mmol). The reaction was stirred at rt for 2 h, then aq HCl (1.0N, 1.3 mL) and H2O (5 mL) were added under stirring. The resulting precipitate was collected via filtration, washed with H2O and dried to yield crude intermediate as an orange solid. This crude intermediate (260 mg) was dissolved into MeOH/EtOAc/95% EtOH and to this solution 10% Pd—C (catalytic) was added. The mixture was vigorously shaken under H2 (50 psi) at rt for 16 h, then filtered through Celite. The filtrate was concentrated and the residue was purified by prep HPLC (H2O/MeOH with 0.1% TFA buffer) to yield 13-cyclohexyl-N-((dimethylamino)sulfonyl)-3-methoxy-6-((4aS,7aS)-octahydro-1H-pyrrolo[3,4-b]pyridin-1-ylcarbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxamide (129 mg, 0.20 mmol, 61%) as a yellow solid. 1H NMR (300 MHz, MeOD) δ ppm 8.11 (s, 1H), 7.93 (d, J=8.8 Hz, 1H), 7.59 (dd, J=8.4, 1.5 Hz, 1H), 7.58 (d, J=8.8 Hz, 1H), 7.18 (dd, J=8.8, 2.6 Hz, 1H), 7.03-7.11 (m, 1H), 6.91-7.00 (m, 1H), 4.99-5.22 (m, 1H), 4.24-4.54 (m, 1H), 3.93 (s, 3H), 3.03 (s, 6H), 2.75-4.02 (m, 8H), 1.12-2.47 (m, 16H). LCMS: m/e 646 (M+H)+, Column C, Gradient time: 2 min, ret time 1.93 min.

Workup

  1. stirringunder stirring
  2. filtrationThe resulting precipitate was collected via filtration
  3. washwashed with H2O
  4. customdried
  5. customto yield crude intermediate as an orange solid
  6. additionwas added
  7. stirringThe mixture was vigorously shaken under H2 (50 psi) at rt for 16 h
  8. filtrationfiltered through Celite
  9. concentrationThe filtrate was concentrated
  10. customthe residue was purified by prep HPLC (H2O/MeOH with 0.1% TFA buffer)

Sources & evidence

ORD record
ord-acff6aee46114f1093c81536c47e2906
Source dataset
uspto-grants-2009_04
Patent number
US07521444B2

Reaction notes

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