Diisopropylethylamine → 6-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-N-methyl-N-((2R,3S,4S,5S)-2,3,4,5,6-pentakis(tert-butyldimethyl silyloxy)hexyl)nicotinamide

HRID 1400874Notes

Reaction equation

HRID 1400874 reaction equation
[CH:1]1([NH:4][C:5](=[O:33])[NH:6][C:7]2[CH:31]=[CH:30][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[CH:29]=[CH:28][C:24]([C:25]([OH:27])=O)=[CH:23][N:22]=5)[S:20][C:13]=34)=[C:9]([F:32])[CH:8]=2)[CH2:3][CH2:2]1.[Si:34]([O:41][C@@H:42]([C@H:46]([O:74][Si:75]([C:78]([CH3:81])([CH3:80])[CH3:79])([CH3:77])[CH3:76])[C@@H:47]([O:66][Si:67]([C:70]([CH3:73])([CH3:72])[CH3:71])([CH3:69])[CH3:68])[C@@H:48]([O:58][Si:59]([C:62]([CH3:65])([CH3:64])[CH3:63])([CH3:61])[CH3:60])[CH2:49][O:50][Si:51]([C:54]([CH3:57])([CH3:56])[CH3:55])([CH3:53])[CH3:52])[CH2:43][NH:44][CH3:45])([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH:1]1([NH:4][C:5](=[O:33])[NH:6][C:7]2[CH:31]=[CH:30][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[CH:29]=[CH:28][C:24]([C:25]([N:44]([CH3:45])[CH2:43][C@@H:42]([O:41][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:35])[CH3:36])[C@H:46]([O:74][Si:75]([C:78]([CH3:81])([CH3:80])[CH3:79])([CH3:76])[CH3:77])[C@@H:47]([O:66][Si:67]([C:70]([CH3:71])([CH3:72])[CH3:73])([CH3:69])[CH3:68])[C@@H:48]([O:58][Si:59]([C:62]([CH3:65])([CH3:64])[CH3:63])([CH3:60])[CH3:61])[CH2:49][O:50][Si:51]([C:54]([CH3:55])([CH3:56])[CH3:57])([CH3:53])[CH3:52])=[O:27])=[CH:23][N:22]=5)[S:20][C:13]=34)=[C:9]([F:32])[CH:8]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 674418286-(7-(4-(3-Cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)nicotinic acidHCID 86658595(2R,3S,4S,5S)-2,3,4,5,6-pentakis(tert-butyldimethylsilyloxy)-N-methylhexan-1-amine

Product 1

HCID 866585946-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-N-methyl-N-((2R,3S,4S,5S)-2,3,4,5,6-pentakis(tert-butyldimethyl silyloxy)hexyl)nicotinamideYield 54%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of acid 225 (220 mg, 0.474 mmol, scheme 54), amine 242 (309 mg, 0.474 mmol) and DIPEA (0.331 mL, 1.895 mmol) in DMF (5 mL) was added HATU reagent (270 mg, 0.710 mmol). The mixture was stirred overnight at room temperature then partitioned between ethyl acetate and water. The organic layer was collected, washed with water, 1M NaOH, and brine, dried over anhydrous MgSO4, filtered and concentrated. The residue was purified by Biotage (MeOH/DCM, 0-15%, SNAP 10 g cartridge) to afford title compound 243 (250 mg, 0.254 mmol, 54% yield) as a white solid. MS: 985.4 (MH+).

Workup

  1. customthen partitioned between ethyl acetate and water
  2. customThe organic layer was collected
  3. washwashed with water, 1M NaOH, and brine
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by Biotage (MeOH/DCM, 0-15%, SNAP 10 g cartridge)

Sources & evidence

ORD record
ord-4619f488fb9d49ce96922983cd05f57e
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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