Water → Tert-butyl {3-[(2-amino[1,3]thiazolo[5,4-d]pyrimidin-5-yl)(cyclopropyl)amino]phenyl)carbamate

HRID 1800716Notes

Reaction equation

HRID 1800716 reaction equation
[CH:1]1([N:4]([C:19]2[N:24]=[C:23]([S:25][C:26]#[N:27])[C:22]([N+:28]([O-])=O)=[CH:21][N:20]=2)[C:5]2[CH:6]=[C:7]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH:8]=[CH:9][CH:10]=2)[CH2:3][CH2:2]1.CN1CCCC1=O.O.[Cl-].[Ca+2].[Cl-]>C(O)C>[NH2:27][C:26]1[S:25][C:23]2[N:24]=[C:19]([N:4]([CH:1]3[CH2:3][CH2:2]3)[C:5]3[CH:6]=[C:7]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH:8]=[CH:9][CH:10]=3)[N:20]=[CH:21][C:22]=2[N:28]=1

Participants

6

Reactant 4

HCID 962WaterHCID 13387N-methyl-2-pyrrolidoneHCID 5284359Calcium ChlorideHCID 86646084Tert-butyl {3-[cyclopropyl(5-nitro-4-thiocyanatopyrimidin-2-yl)amino]phenyl}carbamate

Product 1

HCID 86646085Tert-butyl {3-[(2-amino[1,3]thiazolo[5,4-d]pyrimidin-5-yl)(cyclopropyl)amino]phenyl)carbamateYield 39%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of the above-mentioned crude product of tert-butyl {3-[cyclopropyl(5-nitro-4-thiocyanatopyrimidin-2-yl)amino]phenyl}carbamate in ethanol (60 mL)/1-methylpyrrolidin-2-one (15 mL)/water (10 mL) were added reduced iron (4.29 g, 76.9 mmol) and calcium chloride (8.53 g, 76.9 mmol), and the mixture was stirred at 100° C. for 5 hr, and at room temperature for 2 days. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. To the obtained residue was added water (200 mL), and the mixture was extracted with ethyl acetate (200 mL, 50 mL). The combined organic layer was filtered through a silica gel pad, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=40/60→10/90), and the fractions containing the object product were concentrated under reduced pressure. The obtained residue was washed with ethyl acetate and hexane to give the title compound (2.37 g, 39%) as a gray solid.

Workup

  1. waitat room temperature for 2 days
  2. filtrationThe insoluble material was filtered off
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. additionTo the obtained residue was added water (200 mL)
  5. extractionthe mixture was extracted with ethyl acetate (200 mL, 50 mL)
  6. filtrationThe combined organic layer was filtered through a silica gel pad
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=40/60→10/90)
  9. additionthe fractions containing the object product
  10. concentrationwere concentrated under reduced pressure
  11. washThe obtained residue was washed with ethyl acetate and hexane

Sources & evidence

ORD record
ord-6a370fec83a44bc5abb5452a89934733
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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