Carbonic acid sodium salt (1:2) → (S)-4-(7-(3-(2-methylpyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamide

HRID 1410119

反应方程式

HRID 1410119 反应方程式
Cl[C:2]1[N:3]=[C:4]([NH:11][C:12]2[CH:17]=[C:16]([N:18]3[CH2:22][CH2:21][CH2:20][C@@H:19]3[CH3:23])[CH:15]=[C:14](OC)[CH:13]=2)[C:5]2[N:10]=[CH:9][S:8][C:6]=2[N:7]=1.CC1(C)C(C)(C)OB([C:34]2[CH:42]=[CH:41][C:37]([C:38]([NH2:40])=[O:39])=[CH:36][CH:35]=2)O1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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]>[CH3:23][C@H:19]1[CH2:20][CH2:21][CH2:22][N:18]1[C:16]1[CH:17]=[C:12]([NH:11][C:4]2[C:5]3[N:10]=[CH:9][S:8][C:6]=3[N:7]=[C:2]([C:34]3[CH:42]=[CH:41][C:37]([C:38]([NH2:40])=[O:39])=[CH:36][CH:35]=3)[N:3]=2)[CH:13]=[CH:14][CH:15]=1

参与物

8

反应物 4

HCID 10340Carbonic acid sodium salt (1:2)HCID 27605884-苯甲酰胺硼酸凤梨酯HCID 111557942-二环己基膦-2',4',6'-三异丙基联苯HCID 86671792(S)-5-chloro-N-(3-methoxy-5-(2-methylpyrrolidin-1-yl)phenyl)thiazolo[5,4-d]pyrimidin-7-amine

产物 1

HCID 66550543(S)-4-(7-(3-(2-methylpyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamide收率 21%

试剂、催化剂与溶剂 3

HCID 9811564三(二亚苄基丙酮)二钯催化剂HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂HCID 312751,4-二氧六环溶剂

反应条件

温度
100 °C

实验过程

The mixture of (S)-5-chloro-N-(3-methoxy-5-(2-methylpyrrolidin-1-yl)phenyl)thiazolo[5,4-d]pyrimidin-7-amine (100 mg, 0.29 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (77 mg, 0.29 mmol), Pd2(dba)3 (33 mg, 0.058 mmol), X-Phos (55 mg, 0.116 mmol) and Na2CO3 (123 mg, 1.16 mmol) in dioxane (20 mL) and water (5 mL) was heated to 100° C. with stirring for 16 h under N2. The solvent was removed in vacuo and the resulting residue was purified by column chromatography (DCM:MeOH=80:1) to afford (S)-4-(7-(3-(2-methylpyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamide (26 mg, 21%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 10.02 (s, 1H), 9.39 (s, 1H), 8.46-8.44 (m, 2H), 8.10 (s, 1H), 8.00-7.97 (m, 2H), 7.48-7.39 (m, 2H), 7.29-7.15 (m, 2H), 6.35 (d, 1H, J=7.8 Hz), 3.91 (brs, 1H), 3.41-3.31 (m, 1H), 3.19-3.16 (m, 1H), 2.08-1.98 (m, 2H), 1.71 (brs, 1H), 1.15 (d, 3H, J=6.3 Hz). LC-MS: 431 [M+H]+, tR=1.57 min. HPLC: 95.67% at 214 nm, 95.15% at 254 nm, tR=3.14 min.

后处理

  1. customThe solvent was removed in vacuo
  2. customthe resulting residue was purified by column chromatography (DCM:MeOH=80:1)

来源与证据

ORD记录
ord-54283cd48910422a8344ed11dac65bf4
来源数据集
uspto-grants-2014_12
专利号
US08921383B2

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