Hydrochloric Acid → HCID 57639182、化合物

HRID 2111597ノート

反応式

HRID 2111597 の反応式
[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

参加物

9

反応物 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、化合物

生成物 1

HCID 57639182HCID 57639182、化合物収率 61%

試薬・触媒・溶媒 4

HCID 23938Palladium触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 21584119Ethylacetate methanol溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-acff6aee46114f1093c81536c47e2906
出典データセット
uspto-grants-2009_04
特許番号
US07521444B2

反応ノート

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