Triethylamine → tert-butylN-[1-[[4-chloro-6-(2-phenylethynyl)pyridin-2-yl]amino]-1-oxopropan-2-yl]carbamate

HRID 535427Notes

Reaction equation

[CH3:1][C:2]([O:5][C:6]([NH:8][CH:9]([CH3:13])[C:10]([OH:12])=O)=[O:7])([CH3:4])[CH3:3].[Cl:14][C:15]1[CH:20]=[C:19]([C:21]#[C:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:18]=[C:17]([NH2:29])[CH:16]=1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>O.CN1C(=O)CCC1>[C:2]([O:5][C:6](=[O:7])[NH:8][CH:9]([CH3:13])[C:10]([NH:29][C:17]1[CH:16]=[C:15]([Cl:14])[CH:20]=[C:19]([C:21]#[C:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:18]=1)=[O:12])([CH3:1])([CH3:3])[CH3:4]

Participants

Conditions

Temperature: 40 °C

Procedure

A mixture of 2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid (1.17 g, 6.19 mmol), 4-chloro-6-(2-phenylethynyl)pyridin-2-amine B3a (1.09 g, 4.76 mmol), triethylamine (3.63 ml, 25.7 mmol) HATU (2.89 g, 7.61 mmol) and NMP (3.75 ml) is stirred at 40° C. for 60 h. 2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid (0.72 g, 3.81 mmol) and HATU (1.45 g, 3.81 mmol) is added to the mixture and stirring continued for 48 h at 60° C. At RT water is added and the mixture extracted with DCM. The combined organic layers are dried over MgSO4 and concentrated in vacuo. The product is purified by RP HPLC. Yield: 712 mg (37%). HPLC-MS: M+H=400; tR=2.27 min (*Method—2).

Workup

stirringstirring
waitcontinued for 48 h at 60° C
extractionthe mixture extracted with DCM
dry with materialThe combined organic layers are dried over MgSO4
concentrationconcentrated in vacuo
customThe product is purified by RP HPLC

Sources & evidence

ORD record: ord-df391ad61e0547c8affff740ed09ea1e
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08859541B2

Reaction notes

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