Sodium Hydroxide → HCID 58014986, compound

HRID 1676626Notes

Reaction equation

HRID 1676626 reaction equation
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+]1C2C(=NC=CC=2)[N+]([O-])=N1)C.[C:57]([O:61][C:62]([N:64]1[CH2:67][CH:66]([NH2:68])[CH2:65]1)=[O:63])([CH3:60])([CH3:59])[CH3:58].[OH-].[Na+]>O.ClCCl.C(N(CC)CC)C>[C:57]([O:61][C:62]([N:64]1[CH2:67][CH:66]([NH:68][C:26](=[O:28])[C:25]2[CH:29]=[CH:30][C:22]([NH:21][C:19]3[N:18]=[CH:17][C:8]4[N:9]([CH3:16])[C:10](=[O:15])[C:11]([F:13])([F:14])[CH2:12][N:6]([CH:1]5[CH2:5][CH2:4][CH2:3][CH2:2]5)[C:7]=4[N:20]=3)=[C:23]([O:31][CH3:32])[CH:24]=2)[CH2:65]1)=[O:63])([CH3:60])([CH3:58])[CH3:59]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 1516507Tert-butyl 3-aminoazetidine-1-carboxylateHCID 252529054-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acidHCID 178484293HCID 178484293, compound

Product 1

HCID 58014986HCID 58014986, compoundYield 43.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a mixture of 0.090 g (0.2 mmole) of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid (I-22), 0.0764 g (0.2 mmole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, 3 mL of dichloromethane, 0.08 mL of triethylamine was added followed by 0.0344 g (0.2 mmole) of 3-amino-azetidine-1-carboxylic acid tert-butyl ester. After 2 hours, 6 mL of dichloromethane, 4 mL of water and 0.2 mL of 1M sodium hydroxide was added. The dichloromethane layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with hexanes-ethyl acetate (gradient, 60:40-0:100) to give 0.0523 g of 3-[4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoylamino]-azetidine-1-carboxylic acid tert-butyl ester (I-86).

Workup

  1. additionwas added
  2. dry with materialThe dichloromethane layer was dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography
  6. washeluting with hexanes-ethyl acetate (gradient, 60:40-0:100)

Sources & evidence

ORD record
ord-c765556a81544fd89f704d0f78040047
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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