Diisopropylethylamine → HCID 117749079, compound

HRID 1775873Notes

Reaction equation

HRID 1775873 reaction equation
[NH:1]1[CH2:5][CH2:4][C@H:3]([C:6]([O:8][CH3:9])=[O:7])[CH2:2]1.CCN(C(C)C)C(C)C.[Br:19][C:20]1[CH:21]=[N:22][C:23]([C:26]2[CH:31]=[CH:30][C:29]([CH2:32][C@H:33]([NH:37][C:38]([C:40]3[S:41][C:42]([C:45]([CH3:48])([CH3:47])[CH3:46])=[CH:43][CH:44]=3)=[O:39])[C:34](O)=[O:35])=[CH:28][CH:27]=2)=[N:24][CH:25]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Br:19][C:20]1[CH:25]=[N:24][C:23]([C:26]2[CH:27]=[CH:28][C:29]([CH2:32][C@H:33]([NH:37][C:38]([C:40]3[S:41][C:42]([C:45]([CH3:48])([CH3:47])[CH3:46])=[CH:43][CH:44]=3)=[O:39])[C:34]([N:1]3[CH2:5][CH2:4][C@H:3]([C:6]([O:8][CH3:9])=[O:7])[CH2:2]3)=[O:35])=[CH:30][CH:31]=2)=[N:22][CH:21]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1512682(S)-METHYL PYRROLIDINE-3-CARBOXYLATEHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89620441HCID 89620441, compound

Product 1

HCID 117749079HCID 117749079, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirring solution of methyl (S)-pyrrolidine-3-carboxylate (357.0 mg, 2.16 mmol) in DMF (10 mL) were added DIEA (465.26 mg, 3.60 mmol) and (S)-3-(4-(5-bromopyrimidin-2-yl)phenyl)-2-(5-(tert-butyl)thiophene-2-carboxamido)propanoic acid (700.0 mg, 1.44 mmol). The solution was cooled to 0° C. at ice bath and then HATU (677.55 mg, 2.88 mmol) in 2 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 (3×20 mL) and aqueous NaHCO3 (3×10 mL). The combined organics were dried over MgSO4 and evaporated. The final compound was purified by column chromatography (40% DCM in hexane) to afford 501.0 mg (58%) of methyl (S)-1-((S)-3-(4-(5-bromopyrimidin-2-yl)phenyl)-2-(5-(tert-butyl)thiophene-2-carboxamido)propanoyl)pyrrolidine-3-carboxylate INT-35 as a powder. LCMS-ESI (m/z calculated for C28H31BrN4O4S: 598.1. found 599.3 [M+H]+, tR=3.553 min. (Method 16). 1H NMR (400 MHz, DMSO) δ 9.05 (d, J=1.1 Hz, 2H), 8.77 (dd, J=11.5, 8.3 Hz, 1H), 8.25 (d, J=7.7 Hz, 2H), 7.72 (d, J=3.5 Hz, 1H), 7.46 (d, J=8.3 Hz, 2H), 6.92 (d, J=3.8 Hz, 1H), 4.98-4.73 (m, 1H), 3.88 (dd, J=10.3, 8.0 Hz, 1H), 3.71 (dd, J=15.5, 7.5 Hz, 1H), 3.50 (ddd, J=18.3, 12.2, 5.4 Hz, 2H), 3.38 (dd, J=17.3, 7.6 Hz, 1H), 3.23 (ddd, J=28.0, 15.0, 8.7 Hz, 1H), 3.18-2.85 (m, 3H), 2.17-1.96 (m, 2H), 1.87 (td, J=15.2, 7.4 Hz, 1H), 1.32 (s, 9H).

Workup

  1. temperaturewarmed to RT
  2. stirringwith stirring for 2 hours
  3. extractionThe reaction solution was extracted with DCM (3×20 mL) and aqueous NaHCO3 (3×10 mL)
  4. dry with materialThe combined organics were dried over MgSO4
  5. customevaporated
  6. customThe final compound was purified by column chromatography (40% DCM in hexane)

Sources & evidence

ORD record
ord-9d9d1e571bc84893ab45cb87d2275713
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

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