Water → HCID 86660858, 화합물

HRID 1619686노트

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HRID 1619686 반응식
Br[C:2]1[CH:25]=[CH:24][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([S:13]([NH:16][C:17]3[S:18][CH:19]=[CH:20][N:21]=3)(=[O:15])=[O:14])=[CH:9][C:8]=2[C:22]#[N:23])=[C:4]([C:26]2[N:30]([CH3:31])[N:29]=[CH:28][CH:27]=2)[CH:3]=1.[C:32]([O:36][C:37]([NH:39][CH2:40][C:41]1[CH:42]=[C:43](B(O)O)[CH:44]=[CH:45][CH:46]=1)=[O:38])([CH3:35])([CH3:34])[CH3:33].C(=O)([O-])[O-].[Na+].[Na+].O>O1CCOCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:22]([C:8]1[CH:9]=[C:10]([S:13]([NH:16][C:17]2[S:18][CH:19]=[CH:20][N:21]=2)(=[O:15])=[O:14])[CH:11]=[CH:12][C:7]=1[O:6][C:5]1[CH:24]=[CH:25][C:2]([C:45]2[CH:44]=[CH:43][CH:42]=[C:41]([CH2:40][NH:39][C:37](=[O:38])[O:36][C:32]([CH3:34])([CH3:33])[CH3:35])[CH:46]=2)=[CH:3][C:4]=1[C:26]1[N:30]([CH3:31])[N:29]=[CH:28][CH:27]=1)#[N:23]

참가 물질

7

반응물 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 36846863-(Aminomethyl)benzeneboronic acid, N-BOC protectedHCID 71720541HCID 71720541, 화합물

생성물 1

HCID 86660858HCID 86660858, 화합물수율 61%

시약·촉매·용매 2

HCID 6102075Dichlorobis(triphenylphosphine)palladium촉매HCID 312751,4-Dioxane용매

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온도
120 °C

실험 절차

In a 5 mL microwave vial 4-[4-bromo-2-(1-methyl-1H-pyrazol-5-yl)phenoxy]-3-cyano-N-1,3-thiazol-2-ylbenzene sulfonamide (Patent WO 2010079443, 500 mg, 0.97 mmol) was dissolved in 1,4-dioxane (3 mL) under nitrogen. (3-{[(Tert-butoxycarbonyl)amino]methyl}phenyl)boronic acid (362 mg, 1.44 mmol), bis(triphenylphosphine) palladium (II) dichloride (68 mg, 0.1 mmol), sodium carbonate (204 mg, 1.92 mmol) and water (0.5 mL) were added and the reaction vessel sealed and heated to 120° C. for 45 minutes in the microwave. The reaction mixture was partitioned between ethyl acetate (20 mL) and 0.2M aqueous HCl (20 mL). The organic layer was separated, filtered then concentrated in vacuo. The residue was purified by silica gel column chromatography (ISCO™, 12 g silica, 99:1 DCM:Acetic acid to 90:10:1 DCM:MeOH:Acetic acid gradient) to afford the title compound (380 mg, 61%) as a pale orange solid.

후처리

  1. customthe reaction vessel sealed
  2. customThe reaction mixture was partitioned between ethyl acetate (20 mL) and 0.2M aqueous HCl (20 mL)
  3. customThe organic layer was separated
  4. filtrationfiltered
  5. concentrationthen concentrated in vacuo
  6. customThe residue was purified by silica gel column chromatography (ISCO™, 12 g silica, 99:1 DCM:Acetic acid to 90:10:1 DCM:MeOH:Acetic acid gradient)

출처 및 근거

ORD 기록
ord-dc9e2aeaf9a94f4fbdcef18520a3a030
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08772293B2

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