Diisopropylethylamine → HCID 117748988, compound

HRID 1775877Notes

Reaction equation

HRID 1775877 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6])[CH2:2]1.CCN(C(C)C)C(C)C.[Br:21][C:22]1[CH:23]=[N:24][C:25]([C:28]2[CH:33]=[CH:32][C:31]([CH2:34][C@H:35]([NH:39][C:40]([C:42]3[S:43][C:44]([C:47]([CH3:50])([CH3:49])[CH3:48])=[CH:45][CH:46]=3)=[O:41])[C:36](O)=[O:37])=[CH:30][CH:29]=2)=[N:26][CH:27]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Br:21][C:22]1[CH:27]=[N:26][C:25]([C:28]2[CH:29]=[CH:30][C:31]([CH2:34][C@H:35]([NH:39][C:40]([C:42]3[S:43][C:44]([C:47]([CH3:50])([CH3:49])[CH3:48])=[CH:45][CH:46]=3)=[O:41])[C:36]([N:1]3[CH2:2][CH:3]([C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6])[CH2:4]3)=[O:37])=[CH:32][CH:33]=2)=[N:24][CH:23]=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 21828700tert-Butyl azetidine-3-carboxylateHCID 89620441HCID 89620441, compound

Product 1

HCID 117748988HCID 117748988, compoundYield 89.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirring solution of tert-butyl azetidine-3-carboxylate (64.55 mg, 0.41 mmol) in DMF (1 mL) were added DIEA (169.6 mg, 1.31 mmol), and (S)-3-(4-(5-bromopyrimidin-2-yl)phenyl)-2-(5-(tert-butyl)thiophene-2-carboxamido)propanoic acid (100.0 mg, 0.21 mmol). The solution was cooled to 0° C. at ice bath and then HATU (74.11 mg, 1.31 mmol) in 1 mL DMF solution was slowly added. The reaction was stirred 1 hour at 0° C. and then warmed to RT with stirring for 2 hours. The reaction solution was extracted with DCM (3×10 mL) and aqueous NaHCO3 (3×10 mL). The combined organics were dried over MgSO4 and evaporated. to afford 117.6 mg (85%) of tert-butyl (S)-1-(3-(4-(5-bromopyrimidin-2-yl)phenyl)-2-(5-(tert-butyl)thiophene-2-carboxamido)propanoyl)azetidine-3-carboxylate INT-38 as a solid powder without further purification for next step. LCMS-ESI (m/z) calculated for C30H35BrN4O4S: 626.2. found 627.2 [M+H]+, tR=3.884 min. (Method 16).

Workup

  1. temperaturewarmed to RT
  2. stirringwith stirring for 2 hours
  3. extractionThe reaction solution was extracted with DCM (3×10 mL) and aqueous NaHCO3 (3×10 mL)
  4. dry with materialThe combined organics were dried over MgSO4
  5. customevaporated

Sources & evidence

ORD record
ord-1d8ee5e3f33e4210b7ac115073d30d79
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

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