1-Hydroxybenzotriazole → HCID 90120362, compound

HRID 2202551Notes

Reaction equation

HRID 2202551 reaction equation
[S:1]1[C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=[CH:2]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[NH2:40][C@H:41]([C:51]1[NH:52][C:53]([I:56])=[CH:54][N:55]=1)[CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][C:47]([NH:49][CH3:50])=[O:48]>CN(C=O)C>[I:56][C:53]1[NH:52][C:51]([C@@H:41]([NH:40][C:6]([C:5]2[S:1][CH:2]=[N:3][CH:4]=2)=[O:8])[CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][C:47]([NH:49][CH3:50])=[O:48])=[N:55][CH:54]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 84494Thiazole-5-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 90120278HCID 90120278, compound

Product 1

HCID 90120362HCID 90120362, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of thiazole-5-carboxylic acid (1.5 eq.) in DMF (1 M) was treated with EDC.HCl (1.5 eq.), HOBt (1.5 eq.) and DIPEA (1.5 eq.), Reaction mixture was stirred at room temperature for 10 min and then added to a solution of D7 in DMF (0.33 M). The reaction mixture was stirred at room temperature for 1 h and subsequently partitioned between DCM and sat. aq. NaHCO3. The organic phase was separated and the aqueous phase extracted with DCM. The combined organic extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to give a crude that was purified by flash chromatography (Biotage; 25M; DCM/MeOH) to afford the title compound as a white powder. 1H-NMR (400 MHz, 300K, DMSO-d6) δ 12.25 (br s, 1H), 9.23 (s, 1H), 9.02 (d, 1H, J 8.0 Hz), 8.58 (s, 1H), 7.65 (br s, 1H), 7.23 (s, 1H), 5.05 (m, 1H), 2.55 (d, 3H, J 5.2 Hz), 2.02 (t, 2H, J 7.6 Hz), 1.97 (m, 1H), 1.82 (m, 1H), 1.47 (m, 2H), 1.25 (m, 4H); MS (ES+) C15H20IN5O2S: 462 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 1 h
  2. customsubsequently partitioned between DCM and sat. aq. NaHCO3
  3. customThe organic phase was separated
  4. extractionthe aqueous phase extracted with DCM
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customto give a crude that
  9. customwas purified by flash chromatography (Biotage; 25M; DCM/MeOH)

Sources & evidence

ORD record
ord-1998e256c5a9428b86edc7dcb04a5c65
Source dataset
uspto-grants-2016_06
Patent number
US09365541B2

Reaction notes

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