Acetamidine monohydrochloride → 13-Chloro-4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6,12-triazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene

HRID 1530713Notes

Reaction equation

HRID 1530713 reaction equation
[Cl:1][C:2]1[CH:15]=[C:14]2[C:5]([O:6][CH2:7][CH2:8][N:9]3[C:13]2=[N:12][C:11](I)=[CH:10]3)=[CH:4][N:3]=1.Cl.[C:18]([NH2:21])(=[NH:20])[CH3:19].[CH3:22][C:23]1([CH3:63])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.Cl.[CH:65]([NH:68]N)(C)C>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C(O)(=O)C>[Cl:1][C:2]1[CH:15]=[C:14]2[C:5]([O:6][CH2:7][CH2:8][N:9]3[C:13]2=[N:12][C:11]([C:65]2[N:68]([CH:23]([CH3:63])[CH3:22])[N:21]=[C:18]([CH3:19])[N:20]=2)=[CH:10]3)=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 67170Acetamidine monohydrochlorideHCID 855731-Isopropylhydrazine hydrochlorideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 5820436210-Chloro-2-iodo-5,6-dihydroimidazo[1,2-d]pyrido[4,3-f][1,4]oxazepine

Product 1

HCID 8667148313-Chloro-4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6,12-triazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaeneYield 373.8%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 13-chloro-4-iodo-9-oxa-3,6,12-triazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene (3.00 g, 8.63 mmol), acetamidine hydrochloride (984 mg, 10.4 mmol), Pd(OAc)2 (194 mg, 0.870 mmol), and Xantphos (998 mg, 1.73 mmol) in DMF (20.0 mL) and TEA (5.0 mL) was heated at 40° C. under CO (1 atm) for 3 hrs. After cooling down, isopropylhydrazine hydrochloride (1.05 g, 9.50 mmol) and acetic acid (20.0 mL) were added. The resulting mixture was heated to 65° C. and stirred at this temperature for 1 hr. At the end of reaction, solvents were removed and the residue was poured into water (2000 mL). The solid was collected and washed with acetone to give the desired product (2.23 g, 73% yield) as a yellow solid. LCMS m/z [M+H]+ 345.2.

Workup

  1. temperatureAfter cooling down
  2. temperatureThe resulting mixture was heated to 65° C.
  3. customAt the end of reaction, solvents
  4. customwere removed
  5. additionthe residue was poured into water (2000 mL)
  6. customThe solid was collected
  7. washwashed with acetone

Sources & evidence

ORD record
ord-761abcbf4a364caa8b40364379ffc363
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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