Hydrochloric Acid → HCID 67154029, compound

HRID 1400146Notes

Reaction equation

HRID 1400146 reaction equation
C(OC([NH:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([CH2:21][CH2:22][CH:23]([F:25])[F:24])[C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:11][C:10]=1[C:26](=O)[C:27]([N:29]1[CH2:37][C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:30]1)=[O:28])=O)(C)(C)C.[F-].[Cs+].C[Si]([N:45]=[C:46]=[N:47][Si](C)(C)C)(C)C.Cl.C(=O)(O)[O-]>C(#N)C>[NH2:45][C:46]1[N:47]=[C:26]([C:27]([N:29]2[CH2:30][C:31]3[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:37]2)=[O:28])[C:10]2[C:9](=[CH:14][CH:13]=[C:12]([CH:15]([CH2:21][CH2:22][CH:23]([F:25])[F:24])[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:11]=2)[N:8]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 769Bicarbonate IonHCID 25953Cesium fluorideHCID 70473Bis(trimethylsilyl)carbodiimideHCID 67154010HCID 67154010, compound

Product 1

HCID 67154029HCID 67154029, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1.7 g of ethyl 2-[4-(tert-butoxycarbonylamino)-3-(2-isoindolin-2-yl-2-oxoacetyl)phenyl]-5,5-difluoropentanoate are dissolved in 50 ml of acetonitrile under argon. 486 mg of caesium fluoride and 869 μl of bis(trimethylsilyl)carbodiimide are added to the solution. The mixture is stirred at room temperature for 15 min, and 6 ml of hydrochloric acid (1N) are then added, and the mixture is neutralised using bicarbonate. The aqueous phase is washed three times with 100 ml of ethyl acetate each time. The combined organic phases are dried over sodium sulfate, filtered and evaporated to dryness in vacuo. Yield: 1.4 g (96%) of ethyl 2-[2-amino-4-(isoindoline-2-carbonyl)quinazolin-6-yl]-5,5-difluoropentanoate (oil); LC-MS retention time: 1.71 min (“nonpolar” gradient).

Workup

  1. washThe aqueous phase is washed three times with 100 ml of ethyl acetate each time
  2. dry with materialThe combined organic phases are dried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated to dryness in vacuo

Sources & evidence

ORD record
ord-25427abf3a1142f7a7137ea3fae361ba
Source dataset
uspto-grants-2014_12
Patent number
US08906930B2

Reaction notes

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