1-Boc-Azetidine-3-carboxylic acid → tert-Butyl 3-[({5-[(6,7-dichloro-1-oxo-1,2-dihydropyrrolo[1,2-a]pyrazin-4-yl)methyl]-2-fluorophenyl}amino)carbonyl]azetidine-1-carboxylate

HRID 1172798Notes

Reaction equation

HRID 1172798 reaction equation
[C:1]([N:8]1[CH2:11][CH:10]([C:12]([OH:14])=O)[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.FC(F)(F)C([O-])=O.[Cl:46][C:47]1[N:51]2[C:52]([CH2:57][C:58]3[CH:59]=[CH:60][C:61]([F:65])=[C:62]([NH3+:64])[CH:63]=3)=[CH:53][NH:54][C:55](=[O:56])[C:50]2=[CH:49][C:48]=1[Cl:66]>CN(C1C=CN=CC=1)C.CN(C=O)C.O.CC#N>[Cl:46][C:47]1[N:51]2[C:52]([CH2:57][C:58]3[CH:59]=[CH:60][C:61]([F:65])=[C:62]([NH:64][C:12]([CH:10]4[CH2:9][N:8]([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH2:11]4)=[O:14])[CH:63]=3)=[CH:53][NH:54][C:55](=[O:56])[C:50]2=[CH:49][C:48]=1[Cl:66]

Participants

8

Reactant 3

HCID 27559811-Boc-Azetidine-3-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 866334295-[(6,7-Dichloro-1-oxo-1,2-dihydropyrrolo[1,2-a]pyrazin-4-yl)methyl]-2-fluorobenzenaminium trifluoroacetate

Product 1

HCID 86633428tert-Butyl 3-[({5-[(6,7-dichloro-1-oxo-1,2-dihydropyrrolo[1,2-a]pyrazin-4-yl)methyl]-2-fluorophenyl}amino)carbonyl]azetidine-1-carboxylate

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of 1-Boc-Azetidine-3-carboxilic acid (1.35 eq), HATU (1.35 eq) and DMAP (1.35 eq) in DMF (0.1 M) was stirred at RT for 20 min and then Example 14, N2 (1 eq) was added. The mixture was stirred overnight at RT and the product was isolated by purification by prep RP-HPLC using H2O (+0.1% TFA) and MeCN (+0.1% TFA) as eluents (C18 column). The desired fractions were evaporated to afford the desired compound. 1H NMR (300 MHz, DMSO-d6) δ: 10.89 (1H, d, J=5.6 Hz), 9.80 (1H, s), 7.78-7.69 (1H, m), 7.23-7.14 (2H, m), 7.00-6.91 (1H, m), 6.52 (1H, d, J=5.8 Hz), 4.31 (2H, s), 4.00-3.85 (3H, m), 3.62-3.49 (1H, m), 1.38 (9H, s). MS (ES) C23H23Cl2FN4O4 requires: 508, found: 509 (M+H)+.

Workup

  1. customthe product was isolated by purification by prep RP-HPLC
  2. customThe desired fractions were evaporated

Sources & evidence

ORD record
ord-6298f028900d4d718404328df46307fe
Source dataset
uspto-grants-2010_11
Patent number
US07834015B2

Reaction notes

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