Sodium Hydroxide → HCID 178492720, compound

HRID 1676634Notes

Reaction equation

HRID 1676634 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](O)=[O:27])=[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](=[O:71])[NH:63][C@H:64]1[CH2:69][CH2:68][C@@H:67]([NH2:70])[CH2:66][CH2:65]1)([CH3:60])([CH3:59])[CH3:58].[OH-].[Na+]>O.ClCCl.C(N(CC)CC)C>[C:57]([O:61][C:62](=[O:71])[NH:63][C@H:64]1[CH2:65][CH2:66][C@@H:67]([NH:70][C:26](=[O:27])[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)[CH2:68][CH2:69]1)([CH3:60])([CH3:58])[CH3:59]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 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 178418966HCID 178418966, compoundHCID 178484293HCID 178484293, compound

Product 1

HCID 178492720HCID 178492720, compoundYield 69.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a mixture of 0.112 g (0.15 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), 0.099 g (0.27 mmole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, 2 mL of dichloromethane, 0.3 mL of triethylamine was added followed by 0.051 g (0.24 mmole) of cis-(4-amino-cyclohexyl)-carbamic acid tert-butyl ester. After 3 hours, 4 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, 100:0-0:100) to give 0.0673 g of cis-{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]-cyclohexyl}-carbamic acid tert-butyl ester (I-97).

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-5cc56d51598a45bab6bfc827f8b69c84
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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