Cyclopropanecarbohydrazide → HCID 57513752, compound

HRID 2368444Notes

Reaction equation

HRID 2368444 reaction equation
[F:1][C:2]1[CH:31]=[CH:30][C:5]([C:6]([NH:8][C:9]([CH3:29])([CH3:28])[C:10]([NH:12][C:13]2[S:14][C:15]([C:25]([OH:27])=O)=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[N:17]=2)=[O:11])=[O:7])=[CH:4][CH:3]=1.[CH:32]1([C:35]([NH:37][NH2:38])=O)[CH2:34][CH2:33]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>C1COCC1>[CH:32]1([C:35]2[O:27][C:25]([C:15]3[S:14][C:13]([NH:12][C:10]([C:9]([NH:8][C:6](=[O:7])[C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:31][CH:30]=4)([CH3:29])[CH3:28])=[O:11])=[N:17][C:16]=3[C:18]3[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=3)=[N:38][N:37]=2)[CH2:34][CH2:33]1

Participants

6

Reactant 4

HCID 81396CyclopropanecarbohydrazideHCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57476901HCID 57476901, compound

Product 1

HCID 57513752HCID 57513752, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

To a stirred solution of 2-(2-(4-Fluorobenzamido)-2-methylpropanamido)-4-(4-fluorophenyl)thiazole-5-carboxylic acid (100 mg, 0.224 mmol) and cyclopropanecarbohydrazide (27 mg, 0.27 mmol) were added HATU (128 mg, 0.34 mmol) and TEA (78 uL, 0.56 mmol). Volatiles were removed in vacuo. The residue was taken up in EtOAc and washed with 1N HCl (2×10 mL) followed by sat. NaHCO3 (2×10 mL). Organic layer was dried over magnesium sulfate and filtered. The filtrate was concentrated to dryness to afford a solid. The solid was dissolved in THF (5 mL) and treated with Burgess reagent (68 mg, 0.28 mmol) and heated in microwave at 150° C. for 30 minutes. Purification by silica gel chromatography (30-45% EtOAc/Heptanes) gave the title compound. 1H NMR (400 MHz, DMSO-d6) 0.82 (dd, J=4.74, 2.59 Hz, 3H) 1.08 (dd, J=8.34, 2.78 Hz, 3H) 2.19 (s, 1H) 7.33 (t, J=8.91 Hz, 3H) 7.25 (t, J=8.91 Hz, 3H) 7.71 (dd, J=8.84, 5.56 Hz, 3H) 8.03 (dd, J=8.78, 5.62 Hz, 3H) 8.65 (s, 1H) 12.61 (s, 1H). MS m/z 510.4 (M+H), 508.4 (M−1). HRMS cald for C25H18N2O4S=509.1333, found=509.1334. (M+H)+ 510.4, Rt=1.37 min, method A.

Workup

  1. customVolatiles were removed in vacuo
  2. washwashed with 1N HCl (2×10 mL)
  3. dry with materialOrganic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated to dryness
  6. customto afford a solid
  7. customPurification by silica gel chromatography (30-45% EtOAc/Heptanes)

Sources & evidence

ORD record
ord-bc575e3f79de49e5a6fae76de037ea42
Source dataset
uspto-grants-2014_04
Patent number
US08703761B2

Reaction notes

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