Diisopropylethylamine → (S)-2-(4-bromo-2,6-difluorobenzoylamino)-3-[4-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl]propionic acid propyl ester

HRID 63745Notes

Reaction equation

HRID 63745 reaction equation
[CH2:1]([O:4][C:5](=[O:26])[C@@H:6]([NH2:25])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:15](=[O:24])[N:16]([CH3:23])[C:17](=[O:22])[N:18]([CH3:21])[C:19]=2[CH3:20])=[CH:10][CH:9]=1)[CH2:2][CH3:3].[Br:27][C:28]1[CH:36]=[C:35]([F:37])[C:31]([C:32](O)=[O:33])=[C:30]([F:38])[CH:29]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>>[CH2:1]([O:4][C:5](=[O:26])[C@@H:6]([NH:25][C:32](=[O:33])[C:31]1[C:30]([F:38])=[CH:29][C:28]([Br:27])=[CH:36][C:35]=1[F:37])[CH2:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[C:15](=[O:24])[N:16]([CH3:23])[C:17](=[O:22])[N:18]([CH3:21])[C:19]=2[CH3:20])=[CH:12][CH:13]=1)[CH2:2][CH3:3]

Participants

5

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27732984-Bromo-2,6-difluorobenzoic acidHCID 86691352(S)-2-amino-3-[4-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl]propionic acid propyl ester

Product 1

HCID 86691351(S)-2-(4-bromo-2,6-difluorobenzoylamino)-3-[4-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl]propionic acid propyl ester

Procedure

The title compound was prepared using a similar procedure as described in Example 1, Step 8, starting from (S)-2-amino-3-[4-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl]propionic acid propyl ester (4.67 g, 13 mmol) , 4-bromo-2,6-difluorobenzoic acid (3.12 g, 13.16 mmol), HBTU (4.99 g, 13.16 mmol), and DIPEA (6.8 mL, 39 mmol), and after ISCO column chromatography purification, resulted in an amorphous off-white solid (6.71 g, 89%). ES-HRMS m/e calcd for C26H26BrF2N3O5 (M+H)+ 578.1097, found 578.1096.

Workup

  1. customafter ISCO column chromatography purification

Sources & evidence

ORD record
ord-4cad9bddb4f846cd9560bb286fb9a598
Source dataset
uspto-grants-2016_09
Patent number
US09447035B2

Reaction notes

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