Trimethylsilyl isocyanate → Methyl (4R)-4-(2-bromo-4-fluoro-phenyl)-6-[(7-carbamoyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-yl)methyl]-2-thiazol-2-yl-1,4-dihydropyrimidine-5-carboxylate

HRID 1778488Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@H:9]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:13]([CH2:19][N:20]2[CH:25]3[CH2:26][NH:27][CH2:28][CH:21]2[CH2:22][O:23][CH2:24]3)[NH:12][C:11]([C:29]2[S:30][CH:31]=[CH:32][N:33]=2)=[N:10]1.[N:34]([Si](C)(C)C)=[C:35]=[O:36]>>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@H:9]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:13]([CH2:19][N:20]2[CH:25]3[CH2:26][N:27]([C:35](=[O:36])[NH2:34])[CH2:28][CH:21]2[CH2:22][O:23][CH2:24]3)[NH:12][C:11]([C:29]2[S:30][CH:31]=[CH:32][N:33]=2)=[N:10]1

Participants

Reactant 2

HCID 70696Trimethylsilyl isocyanate

HCID 117706699methyl (4R)-4-(2-bromo-4-fluoro-phenyl)-6-(3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-ylmethyl)-2-thiazol-2-yl-1,4-dihydropyrimidine-5-carboxylate

Product 1

HCID 117706694Methyl (4R)-4-(2-bromo-4-fluoro-phenyl)-6-[(7-carbamoyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-yl)methyl]-2-thiazol-2-yl-1,4-dihydropyrimidine-5-carboxylateYield 70.9%

Procedure

The title compound was prepared in analogy to Example 18 starting from methyl (4R)-4-(2-bromo-4-fluoro-phenyl)-6-(3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-ylmethyl)-2-thiazol-2-yl-1,4-dihydropyrimidine-5-carboxylate 53b (50 mg, 0.09 mmol) and isocyanato(trimethyl)silane (43 mg, 0.37 mmol). 37 mg of the title compound was isolated as a light yellow powder.

Sources & evidence

ORD record: ord-de09d8ccf79d402187dac48be46c729a
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09266904B2

Reaction notes

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