Sodium Carbonate → (S)-2-(1-((6-Amino-5-(3-fluoro-5-hydroxyphenyl)pyrimidin-4-yl)amino)-3-(benzyloxy)propyl)-3-(3,5-difluorophenyl)-4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4]triazine-5-carbonitrile

HRID 1052671Notes

Reaction equation

HRID 1052671 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:20]2[N:25]([C:26]3[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([F:33])[CH:27]=3)[C:24](=[O:34])[C:23]3=[C:35]([C:38]#[N:39])[CH:36]=[CH:37][N:22]3[N:21]=2)[CH2:10][CH2:11][O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:3]=1I.[F:41][C:42]1[CH:43]=[C:44](B(O)O)[CH:45]=[C:46]([OH:48])[CH:47]=1.C(=O)([O-])[O-].[Na+].[Na+]>>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:20]2[N:25]([C:26]3[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([F:33])[CH:27]=3)[C:24](=[O:34])[C:23]3=[C:35]([C:38]#[N:39])[CH:36]=[CH:37][N:22]3[N:21]=2)[CH2:10][CH2:11][O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:3]=1[C:44]1[CH:45]=[C:46]([OH:48])[CH:47]=[C:42]([F:41])[CH:43]=1

Participants

4

Reactant 3

HCID 10340Sodium CarbonateHCID 447173083-Fluoro-5-hydroxybenzeneboronic acidHCID 90103340(S)-2-(1-((6-Amino-5-iodopyrimidin-4-yl)amino)-3-(benzyloxy)propyl)-3-(3,5-difluorophenyl)-4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4]triazine-5-carbonitrile

Product 1

HCID 73776929(S)-2-(1-((6-Amino-5-(3-fluoro-5-hydroxyphenyl)pyrimidin-4-yl)amino)-3-(benzyloxy)propyl)-3-(3,5-difluorophenyl)-4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4]triazine-5-carbonitrileYield 18%

Procedure

(S)-2-(1-((6-Amino-5-iodopyrimidin-4-yl)amino)-3-(benzyloxy)propyl)-3-(3,5-difluorophenyl)-4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4]triazine-5-carbonitrile (12 mg, 0.02 mmol) was treated with (3-fluoro-5-hydroxyphenyl)boronic acid (4.5 mg, 0.03 mmol), sodium carbonate (2 M, 55 μl, 0.11 mmol) and 2′-(dimethylamino)-2-biphenylyl-palladium(II) chloride dinorbornylphosphine complex (2 mg, 0.001 mmol) according to the method described in the Preparation 17. The residue was purified by reverse phase using SP1® Purification System to give 2 mg (18% yield) of the title compound as a white solid. Purity 97%.

Workup

  1. customdescribed in the Preparation 17
  2. customThe residue was purified by reverse phase
  3. custom® Purification System

Sources & evidence

ORD record
ord-e50765a6257d4d419c20a235e38d2ba6
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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