Triethylamine → HCID 67354452, compound

HRID 1676601Notes

Reaction equation

HRID 1676601 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(N(CC)CC)C.[C:64]([O:68][C:69]([N:71]1[CH2:76][CH2:75][C@H:74]([NH2:77])[C@H:73]([O:78][CH3:79])[CH2:72]1)=[O:70])([CH3:67])([CH3:66])[CH3:65]>ClCCl.O.[OH-].[Na+]>[C:64]([O:68][C:69]([N:71]1[CH2:76][CH2:75][CH:74]([NH:77][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:14])([F:13])[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)[CH:73]([O:78][CH3:79])[CH2:72]1)=[O:70])([CH3:67])([CH3:66])[CH3:65]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 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 57362389(3R,4S)-4-Amino-1-boc-3-methoxypiperidineHCID 178484293HCID 178484293, compound

Product 1

HCID 67354452HCID 67354452, compoundYield 62.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 14798Sodium HydroxideSolvent

Procedure

To a mixture of 0.100 g (0.156 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), 0.0654 g (0.17 mmole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, 0.13 mL of triethylamine, and 3 mL of dichloromethane was added followed by 0.0395 g (0.17 mmole) of (rac)-cis-4-amino-3-methoxy-piperidine-1-carboxylic acid tert-butyl ester. The mixture was stirred for 1 hour, then diluted with 4 mL of dichloromethane, 4 mL of water and 0.2 mL of 1M sodium hydroxide. 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, 100:0-0:100) to give 0.0643 g of rac-(3S,4R)-4-[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]-3-methoxy-piperidine-1-carboxylic acid tert-butyl ester (I-56).

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, 100:0-0:100)

Sources & evidence

ORD record
ord-964110a005b04ab5afcd4aa6415b046b
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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