Hydrochloric Acid → HCID 178491827、化合物

HRID 2095631

反応式

HRID 2095631 の反応式
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([O:9][CH3:10])[C:3]=1[C@H:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19](B3OC(C)(C)C(C)(C)O3)[CH:20]=2)[NH:15][CH:14]=1)[CH3:12].[Si]([O:38][C@H:39]1[CH2:44][CH2:43][C@H:42]([N:45]2[C:49]([CH3:50])=[C:48](I)[C:47]([CH3:52])=[N:46]2)[CH2:41][CH2:40]1)(C(C)(C)C)(C)C.C([O-])(O)=O.[Na+].Cl>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.O.O1CCOCC1>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([O:9][CH3:10])[C:3]=1[C@H:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19]([C:48]3[C:47]([CH3:52])=[N:46][N:45]([C@H:42]4[CH2:43][CH2:44][C@H:39]([OH:38])[CH2:40][CH2:41]4)[C:49]=3[CH3:50])[CH:20]=2)[NH:15][CH:14]=1)[CH3:12]

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 670040713-[(S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)-ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridineHCID 178434091HCID 178434091、化合物

生成物 1

HCID 178491827HCID 178491827、化合物

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒2 回HCID 312751,4-Dioxane溶媒

実験手順

A mixture of 3-[(S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)-ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (30.0 mg, 0.0696 mmol), 1-(trans-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-4-iodo-3,5-dimethyl-1H-pyrazole (60.5 mg, 0.139 mmol), Pd(PPh3)4 (4.02 mg, 0.00348 mmol), NaHCO3 (17.6 mg, 0.209 mmol) and 4:1 dioxane:water was heated to 80° C. overnight. 2 M of HCl in H2O (0.5 mL, 1 mmol) was added, and the solution was stirred at rt for 1 h. The material was concentrated in vacuo, redissolved in MeOH (1 mL) and passed through a syringe filter pad for HPLC purification. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=1.42-1.57 (m, 2H), 1.80 (d, J=7.1 Hz, 3H), 1.87-2.02 (m, 3H), 2.03 (s, 3H), 2.04-2.12 (m, 3H), 2.14 (s, 3H), 3.64 (br. s., 3H), 3.66-3.72 (m, 1H), 4.11 (tt, J=11.5, 3.9 Hz, 1H), 5.04-5.14 (m, 1H), 6.89 (dd, J=9.2, 4.2 Hz, 1H), 7.08 (t, J=8.8 Hz, 1H), 7.28 (s, 1H), 7.35 (d, J=1.3 Hz, 1H), 7.95 (br. s., 1H). MS (ES+): m/z=497.21/499.21 (100/50) [MH+]. HPLC: tR=1.40 min (polar—3 min, UPLC-ACQUITY).

後処理

  1. concentrationThe material was concentrated in vacuo
  2. dissolutionredissolved in MeOH (1 mL)
  3. custompassed through a syringe
  4. filtrationfilter pad
  5. customfor HPLC purification
  6. additionThe fractions containing the pure product
  7. concentrationwere concentrated in vacuo

出典と根拠

ORDレコード
ord-b881e631bab5445fb212252af9721ae6
出典データセット
uspto-grants-2013_05
特許番号
US08445510B2

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