Sodium Carbonate → HCID 89689839, compound

HRID 877547Notes

Reaction equation

HRID 877547 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]2[S:9][CH:10]=[C:11]([C:13]([N:15]3[CH2:20][CH2:19][CH2:18][CH:17]([OH:21])[CH2:16]3)=[O:14])[N:12]=2)=[C:4]([NH:22][CH:23]([CH3:25])[CH3:24])[CH:3]=1.[S:26]1[C:30]2[CH:31]=[C:32]([NH2:35])[CH:33]=[CH:34][C:29]=2[N:28]=[CH:27]1.C([O-])([O-])=O.[Na+].[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.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].O>[S:26]1[C:30]2[CH:31]=[C:32]([NH:35][C:2]3[N:7]=[CH:6][C:5]([C:8]4[S:9][CH:10]=[C:11]([C:13]([N:15]5[CH2:20][CH2:19][CH2:18][CH:17]([OH:21])[CH2:16]5)=[O:14])[N:12]=4)=[C:4]([NH:22][CH:23]([CH3:25])[CH3:24])[CH:3]=3)[CH:33]=[CH:34][C:29]=2[N:28]=[CH:27]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 682886-AminobenzothiazoleHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 89689614HCID 89689614, compound

Product 1

HCID 89689839HCID 89689839, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
115 °C

Procedure

(2-(6-chloro-4-(isopropylamino)pyridin-3-yl)thiazol-4-yl)(3-hydroxypiperidin-1-yl)methanone (24a) (100 mg, 0.263 mmol) was dissolved in 1,4-Dioxane (10 mL): H2O (2 mL), to it benzo[d]thiazol-6-amine (0.263 mmol), Na2CO3 (1.05 mmol) and xanthphos (0.105 mmol) were added and degassed for 10 min. Pd2(dba)3 (0.105 mmol) was added and degassed once again for 15 min and heated at 115° C., overnight. The reaction mass was filtered through celite and concentrated to remove solvent. The crude material obtained was purified by column chromatography through silica gel and MeOH: CHCl3 as eluent. The material obtained was further purified by prep. HPLC to obtain the title compound, (2-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)thiazol-4-yl)(3-hydroxypiperidin-1-yl)methanone. 1H NMR: 400 MHz, CD3OD: δ 0.87-0.94 (m, 1H), 1.31-1.36 (m, 6H), 1.62-0.00 (m, 2H), 1.92-2.03 (m, 2H), 3.42-3.43 (m, 1H), 3.75-3.98 (m, 4H), 6.16 (s, 1H), 7.54 (dd, J=2.00, 8.80 Hz, 1H), 7.79 (bs, 1H), 7.91 (s, 1H), 7.97 (d, J=8.80 Hz, 1H), 8.43 (d, J=2.40 Hz, 1H), 8.45 (s, 1H), 9.07 (s, 1H). LC/MS: Ascentis Express C18, 5×2.1 mm-2.7 μm; Solvent A=2% ACN: 98% H2O: 10 mM NH4COOH; Solvent B=98% ACN: 2% H2O: 10 mM NH4COOH; gradient 0-100% B over 3 min; retention time: 1.754 min; LCMS (ES-API), m/z 495.2 (M+H). HPLC: Sunfire C18 (150×4.6 mm), 3.5 micron; Solvent A=5% ACN: 95% H2O: 0.05% TFA pH=2.5; Solvent B=95% ACN: 5% H2O: 0.05% TFA pH=2.5; gradient 0-100% B over 15 min (23 min run time); Flow rate: 1.0 μL/min; Retention time: 5.431 min; Purity: 96.29%.

Workup

  1. customdegassed for 10 min
  2. customdegassed once again for 15 min
  3. filtrationThe reaction mass was filtered through celite and
  4. concentrationconcentrated
  5. customto remove solvent
  6. customThe crude material obtained
  7. customwas purified by column chromatography through silica gel and MeOH
  8. customThe material obtained
  9. customwas further purified by prep

Sources & evidence

ORD record
ord-e9fe7cfa11424a16ac1069f6b153da3c
Source dataset
uspto-grants-2015_03
Patent number
US08987311B2

Reaction notes

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