Trifluoroacetic acid → HCID 131723227, compound

HRID 656583Notes

Reaction equation

HRID 656583 reaction equation
[CH3:1][C:2]1([CH3:30])[O:6][C@@H:5]([CH2:7][O:8]/[N:9]=[C:10]2\[NH:11][C@@H:12]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=3Br)[CH2:13][C:14]3[N:15]=[C:16]([NH2:21])[N:17]=[C:18]([CH3:20])[C:19]\2=3)[CH2:4][O:3]1.[CH3:31][O:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35](B2[O:43][C:42]([CH3:45])([CH3:44])C(C)(C)O2)[N:34]=1.C([O-])([O-])=[O:49].[Na+].[Na+].C(O)(C(F)(F)F)=O>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CC(N(C)C)=O>[CH3:1][C:2]1([CH3:30])[O:6][C@@H:5]([CH2:7][O:8]/[N:9]=[C:10]2\[NH:11][C@@H:12]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=3[C:35]3[CH:36]=[CH:37][CH:38]=[C:33]([O:32][CH3:31])[N:34]=3)[CH2:13][C:14]3[N:15]=[C:16]([NH2:21])[N:17]=[C:18]([CH3:20])[C:19]\2=3)[CH2:4][O:3]1.[OH2:49].[C:42]([C:45]#[N:9])([CH3:44])=[O:43]

Participants

9

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 177505082-Methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 178433351HCID 178433351, compound

Product 2

HCID 131723227HCID 131723227, compoundYield 442.8%HCID 178489730HCID 178489730, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
130 °C

Procedure

To a vial containing 32A (40 mg, 0.083 mmol), 2-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (58 mg, 0.25 mmol), Na2CO3 (0.5 mL, 1.0 mmol), Pd(dppf)2Cl2 (3.4 mg, 0.004 mmol) and DMA (0.5 mL) was heated to 130° C. for 20 min in the microwave. The resultant crude mixture was diluted with EtOAc, and washed with H2O, brine, dried over Na2SO4, and concentrated in vacuo to yield (R,Z)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O—((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl oxime (32) after reverse-phase preparative HPLC (16 mg, 39% yield, 10-70% H2O—AcCN, 0.035% TFA). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 3H) 1.41 (s, 3H) 2.85 (s, 3H) 3.15 (dd, J=17.05, 10.48 Hz, 1H) 3.46 (dd, J=17.18, 3.79 Hz, 1H) 3.70-3.80 (m, 1H) 3.88 (s, 3H) 3.99-4.17 (m, 3H) 4.36-4.49 (m, 1H) 4.90 (dd, J=10.36, 3.54 Hz, 1H) 4.30-5.10 (br, 2H) 5.80 (br, 1H) 6.76 (d, J=8.34 Hz, 1H) 7.02 (d, J=7.33 Hz, 1H) 7.10-7.24 (m, 2H) 7.60 (dd, J=8.59, 5.56 Hz, 1H) 7.68 (t, J=7.83 Hz, 1H). ESI-MS: m/z 509.4 (M+H)+.

Workup

  1. washwashed with H2O, brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b5f69b571ae7417c9c06c5455db3822b
Source dataset
uspto-grants-2011_12
Patent number
US08071766B2

Reaction notes

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