Diisopropylethylamine → HCID 178508770, compound

HRID 386694Notes

Reaction equation

HRID 386694 reaction equation
[NH2:1][C:2]1[C:3]([C:10](/[N:12]=[C:13]2/[NH:14][C:15]3([CH2:22][CH2:21][N:20]([C:23]([C:25]4[CH:26]=[C:27]([S:31]([NH:34][CH2:35][CH2:36][C:37]([OH:39])=[O:38])(=[O:33])=[O:32])[CH:28]=[CH:29][CH:30]=4)=[O:24])[CH2:19][CH2:18]3)[CH2:16][NH:17]/2)=[O:11])=[N:4][C:5]([Cl:9])=[C:6]([NH2:8])[N:7]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.O[CH2:74][C:75]([N:77]1[CH2:81][CH2:80][CH2:79][CH:78]1[C:82]([F:85])([F:84])[F:83])=[O:76]>CN(C=O)C>[O:76]=[C:75]([N:77]1[CH2:81][CH2:80][CH2:79][CH:78]1[C:82]([F:85])([F:83])[F:84])[CH2:74][O:38][C:37](=[O:39])[CH2:36][CH2:35][NH:34][S:31]([C:27]1[CH:28]=[CH:29][CH:30]=[C:25]([C:23]([N:20]2[CH2:21][CH2:22][C:15]3([NH:14]/[C:13](=[N:12]/[C:10]([C:3]4[C:2]([NH2:1])=[N:7][C:6]([NH2:8])=[C:5]([Cl:9])[N:4]=4)=[O:11])/[NH:17][CH2:16]3)[CH2:18][CH2:19]2)=[O:24])[CH:26]=1)(=[O:32])=[O:33]

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 667975172-Hydroxy-1-(2-(trifluoromethyl)pyrrolidin-1-yl)ethanoneHCID 178508768HCID 178508768, compound

Product 1

HCID 178508770HCID 178508770, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 3-(3-{2-[(E)-3,5-Diamino-6-chloro-pyrazine-2-carbonylimino]-1,3,8-triaza-spiro[4.5]decane-8-carbonyl}-benzenesulfonylamino)-propionic acid (step 2) (400 mg, 0.690 mmol) and N,N-diisopropylethylamine (357 mg, 2.76 mmol) in DMF (4 ml) was added HATU (262 mg, 0.690 mmol). The solution was stirred at RT for 15 min, after which time 2-hydroxy-1-(2-(trifluoromethyl)pyrrolidin-1-yl)ethanone (Int. D) (262 mg, 0.690 mmol) in DMF (2 ml) was added. The resulting solution was stirred at RT for 6 days, after which time it was poured onto water (10 ml). A white precipitate formed which was collected by filtration, and washed with iso-hexane (20 ml), and purified by C18 reverse phase chromatography eluting with MeCN/water/0.1% TFA to afford the title product; 1H NMR (400 MHz, DMSO-d6) δ 11.03 (1H, s), 9.37 (1H, s), 9.02 (1H, s), 7.92-7.29 (4H, m), 7.24 (14N, s) 7.12 (14N, s), 6.96 (14N, s), 4.95-3.90 (11H, m), 3.66 (2H, t), 3.41 (2H, t), 3.35 (2H, m), 3.07 (2H, t) 2.20-1.61 (7H, m); LC-MS Rt 0.91 mins; 759.0 [M+H]+, Method 2minLC_v003.

Workup

  1. stirringThe resulting solution was stirred at RT for 6 days
  2. additionafter which time it was poured onto water (10 ml)
  3. customA white precipitate formed which
  4. filtrationwas collected by filtration
  5. washwashed with iso-hexane (20 ml)
  6. custompurified by C18 reverse phase chromatography
  7. washeluting with MeCN/water/0.1% TFA

Sources & evidence

ORD record
ord-6a9f450430ad426a95ee6970779646f7
Source dataset
uspto-grants-2013_02
Patent number
US08372845B2

Reaction notes

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