HCID 50999194, compound → HCID 178513964, compound

HRID 591992Notes

Reaction equation

HRID 591992 reaction equation
[NH2:1][C:2]1[C:7]([NH2:8])=[C:6]([NH:9][C@@H:10]2[C@@H:15]3[CH2:16][C@@H:12]([CH:13]=[CH:14]3)[C@@H:11]2[C:17]([NH2:19])=[O:18])[C:5]([Br:20])=[CH:4][N:3]=1.C(OC([N:28]1[CH2:33][CH2:32][C:31]2([CH2:38][CH2:37][C:36]3[CH:39]=[C:40]([C:43](O)=O)[CH:41]=[CH:42][C:35]=3[O:34]2)[CH2:30][CH2:29]1)=O)(C)(C)C>>[Br:20][C:5]1[C:6]([NH:9][C@@H:10]2[C@@H:15]3[CH2:16][C@@H:12]([CH:13]=[CH:14]3)[C@@H:11]2[C:17]([NH2:19])=[O:18])=[C:7]2[N:8]=[C:43]([C:40]3[CH:39]=[C:36]4[C:35](=[CH:42][CH:41]=3)[O:34][C:31]3([CH2:30][CH2:29][NH:28][CH2:33][CH2:32]3)[CH2:38][CH2:37]4)[NH:1][C:2]2=[N:3][CH:4]=1

Participants

3

Reactant 2

HCID 50999194HCID 50999194, compoundHCID 117701905(1S,2S,3R,4R)-3-(2,3-Diamino-5-bromo-pyridin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide

Product 1

HCID 178513964HCID 178513964, compoundYield 79.9%

Conditions

Temperature
50 °C

Procedure

In a similar fashion to Compound LXXXVII, (1S,2S,3R,4R)-3-(2,3-Diamino-5-bromo-pyridin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide (50 mg, 0.148 mmol) and N-tert-butoxycarbonyl-6-carboxy-3,4-dihydrospiro[2H-1-benzopyran-2,4′-piperidine] (75.4 mg, 0.228 mmol) were reacted. The crude reaction was concentrated, then taken up into 4N HCl/dioxane and heated at 50° C. for 4 hours. The reaction mixture was then concentrated and chromatographed on Gilson HPLC 0-45% CH3CN/H2O. The desired fractions were lyophilized to produce 65 mg (47%) of the title compound as the TFA salt. mp: lyophilate, 1H NMR (300 MHz, DMSO-d6): 13.19 (s, 1H), 8.59 (m, 1H), 8.42 (m, 1H), 8.03 (s, 1H), 7.92 (s, 1H), 7.89 (d, 1H), 7.76 (s, 1H), 7.25 (s, 2H), 7.00 (d, J=8 Hz, 1H), 6.38 (s, 2H), 5.19 (t, J=8 Hz, 1H), 3.23 (m, 2H), 3.14 (m, 2H), 2.88 (m, 3H), 2.78 (s, 1H), 2.62 (d, J=8 Hz, 1H), 2.24 (d, J=8 Hz, 1H), 1.96-1.85 (m, 4H), 1.39 (d, J=8 Hz, 1H). MS: 551 (M+H), HPLC: 1.94 min (G method).

Workup

  1. customThe crude reaction
  2. concentrationwas concentrated
  3. concentrationThe reaction mixture was then concentrated
  4. customchromatographed on Gilson HPLC 0-45% CH3CN/H2O

Sources & evidence

ORD record
ord-54ed6f6c1d1e432596508b02e0e873b1
Source dataset
uspto-grants-2016_01
Patent number
US09238656B2

Reaction notes

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