Benzyl azide → N-((1R,2R)-2-(3-(4-(4-(3-Benzyl-3H-1,2,3-triazol-4-yl)butoxy)phenyl)propylamino)-1,2-diphenylethyl)-4-methylbenzenesulfonamide

HRID 631757Notes

Reaction equation

HRID 631757 reaction equation
[CH2:1]([O:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][CH2:16][NH:17][C@H:18]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C@H:19]([NH:26][S:27]([C:30]2[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=2)(=[O:29])=[O:28])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:10][CH:9]=1)[CH2:2][CH2:3][CH2:4][C:5]#[CH:6].[Na].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[CH2:56]([N:63]=[N+:64]=[N-:65])[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1.[OH-].[NH4+]>CC([O-])=O.CC([O-])=O.[Cu+2].CCOC(C)=O>[CH2:56]([N:63]1[C:5]([CH2:4][CH2:3][CH2:2][CH2:1][O:7][C:8]2[CH:9]=[CH:10][C:11]([CH2:14][CH2:15][CH2:16][NH:17][C@H:18]([C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=3)[C@H:19]([NH:26][S:27]([C:30]3[CH:31]=[CH:32][C:33]([CH3:36])=[CH:34][CH:35]=3)(=[O:29])=[O:28])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:12][CH:13]=2)=[CH:6][N:65]=[N:64]1)[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1

Participants

7

Reactant 4

HCID 12152Benzyl azideHCID 14923Ammonium HydroxideHCID 90152985N-((1R,2R)-2-(3-(4-(Hex-5-ynyloxy)phenyl)propylamino)-1,2-diphenylethyl)-4-methylbenzenesulfonamideHCID 178519209sodium (L)-ascorbate

Product 1

HCID 118434136N-((1R,2R)-2-(3-(4-(4-(3-Benzyl-3H-1,2,3-triazol-4-yl)butoxy)phenyl)propylamino)-1,2-diphenylethyl)-4-methylbenzenesulfonamideYield 95%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a nitrogen purged flask was added the N-((1R,2R)-2-(3-(4-(hex-5-ynyloxy)phenyl)propylamino)-1,2-diphenylethyl)-4-methylbenzenesulfonamide (116 mg, 0.200 mmol), Cu(OAc)2 (7 mg, 0.04 mmol) and sodium-(L)-ascorbate (16 mg, 0.08 mmol) and degassed solution of 1/1 THF/water (5 cm3). To the stirred solution was then added benzyl azide (32 mg, 0.24 mmol). The reaction became a blue colour when stirred and then became cloudy white. The reaction was stirred at room temperature for 48 hours. After this EtOAc (10 cm3) was added followed by ammonium hydroxide (35%) solution. The EtOAc was separated and aqueous phase extracted with further EtOAc (2×10 cm3). The EtOAc phases were combined and washed with further ammonium hydroxide (35%) solution. The EtOAc phases were dried over Na2SO4, filtered and the solvent removed under reduced pressure to leave the product as a white solid (140 mg, 0.19 mmol, 95%). Purification was not necessary. Mp 123-124° C.; [α]D27−25.2 (c 0.25 in CHCl3) (R,R); (found (ESI): M++H, 714.3481 C43H48N5O3S requires M, 714.3472); υmax 2925, 1510, 1454, 1324, 1241, 1155, 1047, 811, 698 cm−1; δH (400 MHz, CDCl3) 7.38-7.34 (4H, m, CHAr), 7.25-7.21 (3H, m, CHAr), 7.13-7.10 (3H, m, CHAr), 7.04-7.00 (5H, m, CHAr), 6.97-6.88 (6H, m, CHAr), 6.75 (2H, d, J 8.5 Hz, CHAr), 6.30 (1H, br s, NH), 5.46 (2H, s, ArCH2NNN), 4.25 (1H, d, J 7.9 Hz, CHNHSO2), 3.93 (2H, t, J 5.7 Hz, CH2OAr), 3.59 (1H, d, J 7.9 Hz, CHNH), 2.76 (2H, t, J 7.0 Hz, CH2CNNN), 2.49-2.38 (3H, m, CH2Ar and CHHNH), 2.31-2.24 (4H, m, CH3 and CHHNH overlapping), 1.84-1.81 (4H, m, CH2CH2CH2CH2OAr), 1.69-1.61 (2H, m, CH2CH2NH); δC (100 MHz, CDCl3) 157.18 (CAr), 148.42 (CAr), 142.72 (CAr), 139.31 (CAr), 138.40 (CAr), 137.09 (CAr), 133.76 (CAr), 129.21 (2 CHAr), 129.12 (2 CHAr), 129.09 (2 CHAr), 128.64 (CHAr), 128.31 (2 CHAr), 128.01 (2 CHAr), 127.93 (2 CHAr), 127.58 (2 CHAr), 127.45 (2 CHAr), 127.28 (CHAr), 127.11 (2 CHAr), 120.72 (CHAr), 114.37 (2 CHAr), 82.82 (CH), 67.76 (CH), 67.52 (CH2), 65.19 (C), 63.14 (CH), 62.18 (C), 54.01 (CH2), 46.44 (CH2), 32.37 (CH2), 31.70 (CH2), 28.88 (CH2), 25.98 (CH2), 25.46 (CH2), 21.46 (CH3); m/z (ESI) 714.3 (M++1).

Workup

  1. customdegassed solution of 1/1 THF/water (5 cm3)
  2. stirringThe reaction was stirred at room temperature for 48 hours
  3. customThe EtOAc was separated
  4. extractionaqueous phase extracted with further EtOAc (2×10 cm3)
  5. washwashed with further ammonium hydroxide (35%) solution
  6. dry with materialThe EtOAc phases were dried over Na2SO4
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-afad4c4ade9e4c8788f7ecae53b1c58e
Source dataset
uspto-grants-2016_04
Patent number
US09321045B2

Reaction notes

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