HRID564630

反应详情

EQUATION

反应方程式

REACTANTS

反应物

HCID176

Acetic Acid

C2H4O2

HCID5049666

Sodium triacetoxyborohydride

C6H10BNaO6

HCID10262201

tert-Butyl (2R)-2-methylpiperazine-1-carboxylate

C10H20N2O2

结构：CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1cccc(C(=O)NCc2ccc(F)c(-c3cccc(C=O)c3)c2)c1

HCID57813252

未命名化合物

PRODUCTS

生成物

结构：CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1cccc(C(=O)NCc2ccc(F)c(-c3cccc(CN4CCN[C@H](C)C4)c3)c2)c1

HCID57813317

未命名化合物

AUXILIARIES

试剂、催化剂与溶剂

溶剂HCID11

1,2-Dichloroethane

C2H4Cl2

PROCEDURE

实验过程

A mixture of N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(6-fluoro-3′-formyl-3-biphenylyl)methyl]-1,3-benzenedicarboxamide (100 mg, 0.000152 mol) in 1,2-dichloroethane (4 mL) with 1,1-dimethylethyl (2R)-2-methyl-1-piperazinecarboxylate (48 mg, 0.00024 mol) and sodium triacetoxyborohydride (68 mg, 0.00032 mol) and AcOH (12 μL) was placed on an oscillating shaker overnight at room temperature. The reaction was quenched with sat. aq. NaHCO3, then extracted with 1,2-dichloroethane (2×). Combined organic extracts were washed with sat. aq. NaCl and dried (Na2SO4) and concentrated to a residue. The crude product was taken up in 1,2-dichloroethane (10 mL) containing 25% TFA and allowed to stand at room temperature for 1.5 h. LC-MS showed the reaction to be complete and the solution stripped to dryness. Purification was carried out on Gilson HPLC instrument with acetonitrile-water (0.1% TFA) gradient; C18-RP Column. Fractions containing the clean desired product were combined; diluted with EtOAc; washed with sat. aq. NaHCO3; and the aq. phase was back-extracted with EtOAc. Combined organic extracts were washed with sat. aq. NaCl and dried (Na2SO4) and concentrated to a residue. It was taken up in a small amount of 1,2-dichloroethane and transferred to a vial and pumped down to afford the title compound as an ivory colored solid [62.1 mg (53%)]. LC-MS m/z 747.3 (M+H)+.

WORKUP

后处理

customwas placed on an oscillating shaker overnight at room temperature
customThe reaction was quenched with sat. aq. NaHCO3
extractionextracted with 1,2-dichloroethane (2×)
washCombined organic extracts were washed with sat. aq. NaCl
dry with materialdried (Na2SO4)
concentrationconcentrated to a residue
additioncontaining 25% TFA
customthe reaction
customPurification
additionFractions containing the clean desired product
additiondiluted with EtOAc
washwashed with sat. aq. NaHCO3
extractionand the aq. phase was back-extracted with EtOAc
washCombined organic extracts were washed with sat. aq. NaCl
dry with materialdried (Na2SO4)
concentrationconcentrated to a residue

来源与证据

来源类型: Open Reaction Database
ORD 记录: ord-ad49e1b9134b4f0b92ce3a0906c5374a
来源数据集: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
专利: US08067408B2
来源说明: uspto-grants-2011_11

反应 SMILES

[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:48][CH3:49])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([NH:31][CH2:32][C:33]4[CH:34]=[C:35]([C:40]5[CH:45]=[CH:44][CH:43]=[C:42]([CH:46]=O)[CH:41]=5)[C:36]([F:39])=[CH:37][CH:38]=4)=[O:30])[CH:24]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].[CH3:50][C@@H:51]1[CH2:56][NH:55][CH2:54][CH2:53][N:52]1C(OC(C)(C)C)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CC(O)=O>ClCCCl>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:48][CH3:49])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([NH:31][CH2:32][C:33]4[CH:34]=[C:35]([C:40]5[CH:45]=[CH:44][CH:43]=[C:42]([CH2:46][N:55]6[CH2:54][CH2:53][NH:52][C@H:51]([CH3:50])[CH2:56]6)[CH:41]=5)[C:36]([F:39])=[CH:37][CH:38]=4)=[O:30])[CH:24]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]