Hydrochloric Acid → Hydrochloric Acid

HRID 2095717노트

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HRID 2095717 반응식
Br[C:2]1[CH:3]=[C:4]2[C:10]([C@@H:11]([C:13]3[C:18]([O:19][CH:20]([F:22])[F:21])=[CH:17][CH:16]=[C:15]([F:23])[C:14]=3[Cl:24])[CH3:12])=[CH:9][N:8](C(OC(C)(C)C)=O)[C:5]2=[N:6][CH:7]=1.CC1(C)[O:37][C@H:36]([CH2:38][N:39]2[C:43]([CH3:44])=[C:42](B3OC(C)(C)C(C)(C)O3)[CH:41]=[N:40]2)[CH2:35][O:34]1.C([O-])([O-])=O.[K+].[K+].O.[ClH:62].CCOCC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[Cl:24][C:14]1[C:15]([F:23])=[CH:16][CH:17]=[C:18]([O:19][CH:20]([F:21])[F:22])[C:13]=1[C@H:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:42]3[CH:41]=[N:40][N:39]([CH2:38][C@@H:36]([OH:37])[CH2:35][OH:34])[C:43]=3[CH3:44])[CH:3]=2)[NH:8][CH:9]=1)[CH3:12].[ClH:62]

참가 물질

10

반응물 6

HCID 313Hydrochloric Acid2회HCID 962Water2회HCID 3283Diethyl EtherHCID 11430Potassium CarbonateHCID 67003931tert-Butyl 5-bromo-3-{(1S)-1-[2-chloro-6-(difluoromethoxy)-3-fluorophenyl]ethyl}-1H-pyrrolo[2,3-b]pyridine-1-carboxylateHCID 670040821-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

생성물 2

HCID 313Hydrochloric AcidHCID 54673762(2R)-3-[4-(3-{(1S)-1-[2-Chloro-6-(difluoromethoxy)-3-fluorophenyl]ethyl}-1H-pyrrolo[2,3-b]pyridin-5-yl)-5-methyl-1H-pyrazol-1-yl]propane-1,2-diol

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 312751,4-Dioxane용매

실험 절차

A mixture of tert-butyl 5-bromo-3-{(1S)-1-[2-chloro-6-(difluoromethoxy)-3-fluorophenyl]ethyl}-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (50.0 mg, 0.0962 mmol), 1-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (46.50 mg, 0.1443 mmol), Pd(PPh3)4 (5.558 mg, 0.004810 mmol), K2CO3 (39.89 mg, 0.2886 mmol) and 4:1 dioxane:H2O (2 mL, 20 mmol) was heated to 95° C. for 2 h. The solution was cooled to rt, and 12 M of HCl in H2O (0.08017 mL, 0.9620 mmol) was added. The material was concentrated in vacuo, and extracted with DCM and sat. NaHCO3. The organic layer was dry-loaded onto silica gel and purified via column chromatography, eluting with 3-6% (7N NH3 in MeOH)/DCM. The fractions containing the pure product were concentrated in vacuo, redissolved in MeOH, and 2.0 M of HCl in Et2O (0.4810 mL, 0.9620 mmol) was added at rt. The solution was concentrated in vacuo to afford the title compound as an HCl salt. 1H NMR (400 MHz, CD3OD): δ=1.85 (d, J=7.1 Hz, 3H), 2.27 (s, 3H), 3.52-3.63 (m, 2H), 4.00-4.08 (m, 1H), 4.11-4.19 (m, 1H), 4.26 (dd, J=14.1, 4.3 Hz, 1H), 5.12 (q, J=7.2 Hz, 1H), 6.44 (br. s., 1H), 7.14 (dd, J=8.8, 4.5 Hz, 1H), 7.20 (t, J=8.7 Hz, 1H), 7.37-7.43 (m, 2H), 7.52 (s, 1H), 8.16 (d, J=2.0 Hz, 1H). MS (ES+): m/z=495.11/497.11 (100/50) [MH+]. HPLC: tR=1.29 min (polar—3 min, UPLC-ACQUITY).

후처리

  1. concentrationThe material was concentrated in vacuo
  2. extractionextracted with DCM and sat. NaHCO3
  3. custompurified via column chromatography
  4. washeluting with 3-6% (7N NH3 in MeOH)/DCM
  5. additionThe fractions containing the pure product
  6. concentrationwere concentrated in vacuo
  7. dissolutionredissolved in MeOH
  8. concentrationThe solution was concentrated in vacuo

출처 및 근거

ORD 기록
ord-0ba8418bffbf42648709c119706e9012
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08445510B2

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