5-Amino-3-phenylisoxazole → (R)-2-(4-cyano-2-fluoro-5-(3-phenylisoxazol-5-ylamino)phenylamino)-3-cyclopropylpropanamide

HRID 2201148

反応式

Br[C:2]1[C:3]([C:18]#[N:19])=[CH:4][C:5]([F:17])=[C:6]([NH:8][C@H:9]([CH2:13][CH:14]2[CH2:16][CH2:15]2)[C:10]([NH2:12])=[O:11])[CH:7]=1.[NH2:20][C:21]1[O:25][N:24]=[C:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:22]=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:18]([C:3]1[C:2]([NH:20][C:21]2[O:25][N:24]=[C:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:22]=2)=[CH:7][C:6]([NH:8][C@H:9]([CH2:13][CH:14]2[CH2:16][CH2:15]2)[C:10]([NH2:12])=[O:11])=[C:5]([F:17])[CH:4]=1)#[N:19]

参加物

実験手順

A mixture of (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-cyclopropylpropanamide (150 mg, 0.460 mmol), 5-amino-3-phenylisoxazole (100 mg, 0.625 mmol), sodium phenoxide trihydrate (100 mg, 0.588 mmol), xantphos (60 mg, 0.103 mmol) and Pd2 dba3 (40 mg, 0.043 mmol) in dioxane (3 mL) was degassed with Ar, then was stirred at 120 C for 18 h. HOAc (0.5 mL) was added. The mixture was concentrated in vacuo. The residue was purified by HPLC to give (R)-2-(4-cyano-2-fluoro-5-(3-phenylisoxazol-5-ylamino)phenylamino)-3-cyclopropylpropanamide (75 mg).

後処理

customwas degassed with Ar
additionHOAc (0.5 mL) was added
concentrationThe mixture was concentrated in vacuo
customThe residue was purified by HPLC

出典と根拠

ORDレコード: ord-1c37b418d7fd4d64abbd0f351e1e0dec
出典データセット: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
特許番号: US09359375B2

反応式

参加物

反応物 4

生成物 1

試薬・触媒・溶媒 2

実験手順

後処理

出典と根拠

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