Potassium Phosphate, Tribasic → HCID 71247866, compound

HRID 1055139Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]([C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:10][CH:11]([OH:14])[CH2:12][OH:13])[C:5]([F:19])=[CH:4][N:3]=1.[F:20][C:21]1[CH:22]=[C:23]2[C:29](B3OC(C)(C)C(C)(C)O3)=[CH:28][N:27]([S:39]([C:42]3[CH:47]=[CH:46][C:45]([CH3:48])=[CH:44][CH:43]=3)(=[O:41])=[O:40])[C:24]2=[N:25][CH:26]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:19][C:5]1[C:6]([NH:8][C@@H:9]([C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:10][CH:11]([OH:14])[CH2:12][OH:13])=[N:7][C:2]([C:29]2[C:23]3[C:24](=[N:25][CH:26]=[C:21]([F:20])[CH:22]=3)[N:27]([S:39]([C:42]3[CH:47]=[CH:46][C:45]([CH3:48])=[CH:44][CH:43]=3)(=[O:40])=[O:41])[CH:28]=2)=[N:3][CH:4]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of (4R)-4-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]-5,5-dimethyl-hexane-1,2-diol, 189a, (0.090 g, 0.309 mmol), 5-fluoro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine (0.167 g, 0.401 mmol) and K3PO4 (0.196 g, 0.926 mmol) in 2-Methyl THF (15 mL) and H2O (2 mL) was degassed under a stream of nitrogen for 45 minutes. To the reaction mixture was added X-phos (0.018 g, 0.037 mmol) and Pd2(dba)3 (0.007 g, 0.008 mmol). The reaction mixture was stirred at 120° C. in a pressure tube for 2 hours. The aqueous phase was removed and the organic phase was filtered through a pad of celite and concentrated in vacuo. The resulting crude material was purified by silica gel chromatography (60% EtOAc/Hexanes) to afford 140 mg of the desired product, 191a: 1H NMR (400 MHz, CDCl3) δ 8.51 (dt, J=7.6, 3.8 Hz, 1H), 8.48 (s, 1H), 8.32 (d, J=1.7 Hz, 1H), 8.12 (dd, J=7.2, 5.7 Hz, 3H), 7.30 (d, J=8.1 Hz, 2H), 4.99 (d, J=10.1 Hz, 1H), 4.42-4.28 (m, 2H), 3.72-3.47 (m, 3H), 2.40 (s, 3H), 2.19-2.09 (m, 1H), 1.97-1.83 (m, 1H), 1.49-1.34 (m, 1H), 1.06 (s, 9H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=3.53 minutes (M+H) 546.49.

Workup

customThe aqueous phase was removed
filtrationthe organic phase was filtered through a pad of celite
concentrationconcentrated in vacuo
customThe resulting crude material was purified by silica gel chromatography (60% EtOAc/Hexanes)

Sources & evidence

ORD record: ord-17f1dcf6df2b45c18f75d645f6bbeb2c
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394302B2

Reaction notes

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