Water → 2-[(1-{Bis[(tert-butoxy)carbonyl]amino}isoquinolin-6-yl)amino]-15,15-difluoro-4,17,20-trimethyl-3,12-dioxo-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10 (21),16,19-hexaene-7-carboxylic acid

HRID 708823Notes

Reaction equation

HRID 708823 reaction equation
[Li+].[OH-].O.[C:4]([O:8][C:9]([N:11]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[C:12]1[C:21]2[C:16](=[CH:17][C:18]([NH:22][CH:23]3[C:40](=[O:41])[N:39]([CH3:42])[CH2:38][C:37]4[CH:43]=[C:33]([CH:34]=[CH:35][C:36]=4[C:44]([O:46]C)=[O:45])[NH:32][C:31](=[O:48])[O:30][CH2:29][C:28]([F:50])([F:49])[C:27]4[C:51]([CH3:53])=[CH:52][C:24]3=[CH:25][C:26]=4[CH3:54])=[CH:19][CH:20]=2)[CH:15]=[CH:14][N:13]=1)=[O:10])([CH3:7])([CH3:6])[CH3:5].S(=O)(=O)(O)[O-].[Na+]>O1CCOCC1>[C:4]([O:8][C:9]([N:11]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[C:12]1[C:21]2[C:16](=[CH:17][C:18]([NH:22][CH:23]3[C:40](=[O:41])[N:39]([CH3:42])[CH2:38][C:37]4[CH:43]=[C:33]([CH:34]=[CH:35][C:36]=4[C:44]([OH:46])=[O:45])[NH:32][C:31](=[O:48])[O:30][CH2:29][C:28]([F:50])([F:49])[C:27]4[C:26]([CH3:54])=[CH:25][C:24]3=[CH:52][C:51]=4[CH3:53])=[CH:19][CH:20]=2)[CH:15]=[CH:14][N:13]=1)=[O:10])([CH3:6])([CH3:7])[CH3:5]

Participants

6

Reactant 4

HCID 962WaterHCID 3939Lithium HydroxideHCID 516919Sodium BisulfateHCID 118093104Methyl 2-[(1-{bis[(tert-butoxy)carbonyl]amino}isoquinolin-6-yl)amino]-15,15-difluoro-4,17,20-trimethyl-3,12-dioxo-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10 (21),16,19-hexaene-7-carboxylate

Product 1

HCID 1180986912-[(1-{Bis[(tert-butoxy)carbonyl]amino}isoquinolin-6-yl)amino]-15,15-difluoro-4,17,20-trimethyl-3,12-dioxo-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10 (21),16,19-hexaene-7-carboxylic acidYield 100%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a flask containing LiOH (38.7 mg, 1.617 mmol) was added water (8 mL). A solution of 4C (130 mg, 0.162 mmol) in dioxane (10 mL) was added and the reaction was stirred for 4.5 h. The reaction was partially evaporated to remove the dioxane then transferred to a funnel using H2O (3 mL) and EtOAc (3 mL). To the mixture was added 1N sodium bisulfate (3.23 mL, 3.23 mmol) followed by extraction with EtOAc (4×8 mL). The combined organics were dried (Na2SO4), filtered and concentrated to leave 4D (128 mg, 90% yield) as a white solid. About 10% of the material is mono-boc compound by LC/MS. 19F and MS are consistent with the desired product.

Workup

  1. customThe reaction was partially evaporated
  2. customto remove the dioxane
  3. customthen transferred to a funnel
  4. extractionfollowed by extraction with EtOAc (4×8 mL)
  5. dry with materialThe combined organics were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-598f262a4aef4aff92131a0ddbab536a
Source dataset
uspto-grants-2015_11
Patent number
US09174974B2

Reaction notes

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