1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → (R)-2-(4-cyano-3-(3-methylisothiazol-5-ylamino)phenylamino)-3-(thiophen-2-yl)propanamide

HRID 2201126

반응식

HRID 2201126 반응식
Br[C:2]1[CH:3]=[C:4]([NH:10][C@H:11]([CH2:15][C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)[C:12]([NH2:14])=[O:13])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].Cl.[NH2:22][C:23]1[S:27][N:26]=[C:25]([CH3:28])[CH:24]=1.O.O.O.[O-]C1C=CC=CC=1.[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:8]([C:7]1[CH:6]=[CH:5][C:4]([NH:10][C@H:11]([CH2:15][C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)[C:12]([NH2:14])=[O:13])=[CH:3][C:2]=1[NH:22][C:23]1[S:27][N:26]=[C:25]([CH3:28])[CH:24]=1)#[N:9]

참가 물질

7

반응물 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 23681143Sodium Phenoxide TrihydrateHCID 67508155(R)-2-(3-bromo-4-cyanophenylamino)-3-(thiophen-2-yl)propanamide

생성물 1

HCID 67508797(R)-2-(4-cyano-3-(3-methylisothiazol-5-ylamino)phenylamino)-3-(thiophen-2-yl)propanamide수율 33.9%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

실험 절차

A mixture of (R)-2-(3-bromo-4-cyanophenylamino)-3-(thiophen-2-yl)propanamide (35 mg, 0.100 mmol), 5-amino-3-methylisothiazole hydrochloride (25 mg, 0.166 mmol), sodium phenoxide trihydrate (52 mg, 0.305 mmol), xantphos (14 mg, 0.024 mmol) and Pd2 dba3 (10 mg, 0.010 mmol) in dioxane (2 mL) was degassed with argon, then was heated by microwave at 170 C for 30 min. The mixture was concentrated in vacuo. The residue was purified by HPLC to give (R)-2-(4-cyano-3-(3-methylisothiazol-5-ylamino)phenylamino)-3-(thiophen-2-yl)propanamide (13 mg).

후처리

  1. customwas degassed with argon
  2. temperaturewas heated by microwave at 170 C for 30 min
  3. concentrationThe mixture was concentrated in vacuo
  4. customThe residue was purified by HPLC

출처 및 근거

ORD 기록
ord-06fbf081666d425e8da0bae9566d859b
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09359375B2

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