Sodium Azide → Ethyl 1-(5-(7-amino-2-(3-ethylureido)benzo[d]thiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate

HRID 712308Notes

Reaction equation

HRID 712308 reaction equation
Br[C:2]1[C:10]2[S:9][C:8]([NH:11][C:12]([NH:14][CH2:15][CH3:16])=[O:13])=[N:7][C:6]=2[CH:5]=[C:4]([C:17]2[CH:18]=[N:19][C:20]([N:23]3[CH2:28][CH2:27][C:26]([CH3:34])([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:25][CH2:24]3)=[N:21][CH:22]=2)[CH:3]=1.[N-:35]=[N+]=[N-].[Na+]>CS(C)=O.O.[Cu]I.O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>[NH2:35][C:2]1[C:10]2[S:9][C:8]([NH:11][C:12]([NH:14][CH2:15][CH3:16])=[O:13])=[N:7][C:6]=2[CH:5]=[C:4]([C:17]2[CH:18]=[N:19][C:20]([N:23]3[CH2:28][CH2:27][C:26]([CH3:34])([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:25][CH2:24]3)=[N:21][CH:22]=2)[CH:3]=1

Participants

6

Reactant 2

HCID 33557Sodium AzideHCID 86663956Ethyl 1-(5-(7-bromo-2-(3-ethylureido)benzo[d]thiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate

Product 1

HCID 86664019Ethyl 1-(5-(7-amino-2-(3-ethylureido)benzo[d]thiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylateYield 92.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 23667548Sodium AscorbateCatalystHCID 23503278(Methanesulfinyl)methane--water (1/1)Solvent

Conditions

Temperature
110 °C

Procedure

Ethyl 1-(5-(7-bromo-2-(3-ethylureido)benzo[d]thiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate (306 mg, 0.56 mmol), trans-(1R,2R)—N,N′-bismethyl-1,2-cyclohexane (24 mg, 0.17 mmol), sodium azide (73 mg, 1.12 mmol) and sodium ascorbate (6 mg, 0.028 mmol) were stirred in DMSO-water 1:1 (3 ml) which had been degassed with N2. CuI (1.1 mg, 0.0056 mmol) was added and the tube purged with N2, sealed and heated to 110° C. for 2 h. The mixture turned black and evolution of gas was observed. LCMS after this time indicated 34% conversion to the desired amine and starting material remaining. Additional equivalents of all reagents were added and the reaction was heated to 110° C. for a further 2 h. LCMS after this time indicated 75% conversion to the desired material. The solvents were removed under reduced pressure and the resulting residue was triturated with water. The resulting solid was isolated by filtration and dried to afford the crude product (250 mg, 73% purity by LCMS) (92%). This material was used directly in the next step without further purification.

Workup

  1. customhad been degassed with N2
  2. customthe tube purged with N2
  3. customsealed
  4. additionAdditional equivalents of all reagents were added
  5. temperaturethe reaction was heated to 110° C. for a further 2 h
  6. customThe solvents were removed under reduced pressure
  7. customthe resulting residue was triturated with water
  8. customThe resulting solid was isolated by filtration
  9. customdried

Sources & evidence

ORD record
ord-34001a0e2dea4116842fe6f418ac0b7c
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

Loading…