Sodium Carbonate → HCID 86603175, compound

HRID 1818946Notes

Reaction equation

HRID 1818946 reaction equation
Br[C:2]1[S:10][C:9]2[C:8]([NH:11][CH2:12][CH2:13][C:14]3[S:18][C:17]([NH:19][C:20]([NH:22][C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=4)=[O:21])=[N:16][CH:15]=3)=[N:7][CH:6]=[N:5][C:4]=2[CH:3]=1.[C:33]([O:37][C:38]([N:40]1[CH2:45][CH:44]=[C:43](B2OC(C)(C)C(C)(C)O2)[CH2:42][CH2:41]1)=[O:39])([CH3:36])([CH3:35])[CH3:34].C([O-])([O-])=O.[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C=O)C.O>[C:33]([O:37][C:38]([N:40]1[CH2:41][CH:42]=[CH:43][CH2:44][CH2:45]1)=[O:39])([CH3:36])([CH3:34])[CH3:35].[N:5]1[C:4]2[CH:3]=[CH:2][S:10][C:9]=2[C:8]([NH:11][CH2:12][CH2:13][C:14]2[S:18][C:17]([NH:19][C:20]([NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:30])([F:31])[F:32])[CH:24]=3)=[O:21])=[N:16][CH:15]=2)=[N:7][CH:6]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 86603176HCID 86603176, compound

Product 1

HCID 86603175HCID 86603175, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Procedure

A 100 mL vial was charged with compound 34.1 (125 mg, 100 mol %), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (86 mg, 120 mole %), and PdCl2(PPh3)2 (33 mg, 20 mol %). To this was added DMF/H2O (4:1, 1 mL) along with 2N Na2CO3 (0.3 mL). The vial was flushed with nitrogen, sealed, and subjected to microwave irradiation (10 minutes, 300 W, 100° C.). The contents were cooled and concentrated in vacuo. The resulting residue was purified by reverse phase HPLC (aqueous 0.1% CF3COOH/MeCN gradient) resulting in a 1:1 mixture of 1-{5-[2-(thieno[3,2-d]pyrimidin-4-ylamino)-ethyl]-thiazol-2-yl}-3-(3-trifluoromethyl-phenyl)-urea; compound with 3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (compound 50.1) and the titled compound. This mixture was dissolved in 4N HCl/dioxane (2 mL), stirred at room temperature for 15 minutes, and concentrated in vacuo to provide exclusively the HCl salt of the titled compound as a yellow powder LCMS [M+H]+ m/z 546.1.

Workup

  1. customThe vial was flushed with nitrogen
  2. customsealed
  3. customsubjected to microwave irradiation (10 minutes, 300 W, 100° C.)
  4. temperatureThe contents were cooled
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by reverse phase HPLC (aqueous 0.1% CF3COOH/MeCN gradient)

Sources & evidence

ORD record
ord-152480440e3d4306b356896252d6a03b
Source dataset
uspto-grants-2009_10
Patent number
US07601725B2

Reaction notes

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