2-Aminothiazole → HCID 86664016, compound

HRID 712302Notes

Reaction equation

HRID 712302 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.[NH2:35][C:36]1[S:37][CH:38]=[CH:39][N:40]=1.C(N(CC)CC)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:69][C:51]2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[S:37]1[CH2:38][CH2:39][N:40]=[C:36]1[NH:35][C:51]([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:22]=[N:21][C:20]([N:23]3[CH2:24][CH2:25][C:26]([CH3:34])([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:27][CH2:28]3)=[N:19][CH:18]=2)[CH:3]=1)=[O:69]

Participants

7

Reactant 4

HCID 21552-AminothiazoleHCID 8471TriethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86663956Ethyl 1-(5-(7-bromo-2-(3-ethylureido)benzo[d]thiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate

Product 1

HCID 86664016HCID 86664016, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

Ethyl 1-(5-(7-bromo-2-(3-ethylureido)benzo[d]thiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate (200 mg, 0.37 mmol) and 2-aminothiazole (111 mg, 1.11 mmol) were stirred in DMF (3 ml) and triethylamine (3 ml) was added. Carbon monoxide was bubbled through the mixture for 10 min. Xantphos (86.3 mg, 0.15 mmol) and palladium (II) acetate (18 mg, 0.08 mmol) were added and the reaction was purged with carbon monoxide, sealed then heated to 90° C. for 18 h. The reaction was allowed to cool and the solvents removed under reduced pressure. The resulting residue was triturated with water causing a solid to precipitate which was isolated by filtration to afford the target material (185 mg, 80% pure by LC-MS) (86%) after drying in a vacuum oven. This material was used directly in the next step with no further purification.

Workup

  1. customCarbon monoxide was bubbled through the mixture for 10 min
  2. customthe reaction was purged with carbon monoxide
  3. customsealed
  4. temperatureto cool
  5. customthe solvents removed under reduced pressure
  6. customThe resulting residue was triturated with water causing a solid
  7. customto precipitate which
  8. customwas isolated by filtration
  9. customto afford the target material (185 mg, 80% pure by LC-MS) (86%)
  10. customafter drying in a vacuum oven
  11. customThis material was used directly in the next step with no further purification

Sources & evidence

ORD record
ord-59b1d8ccbdde492e983e5935f4a57058
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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