Hydrochloric Acid → HCID 57639182, 화합물

HRID 2111597노트

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HRID 2111597 반응식
[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

참가 물질

9

반응물 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 448909431H-Pyrrolo[3,4-b]pyridine, octahydro-6-(phenylmethyl)-, hydrochloride (1:2), (4aS,7aS)-HCID 59682115HCID 59682115, 화합물

생성물 1

HCID 57639182HCID 57639182, 화합물수율 61%

시약·촉매·용매 4

HCID 23938Palladium촉매HCID 962Water용매HCID 6228Dimethylformamide용매HCID 21584119Ethylacetate methanol용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-acff6aee46114f1093c81536c47e2906
출처 데이터셋
uspto-grants-2009_04
특허 번호
US07521444B2

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