Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → HCID 66785824, compound

HRID 1096676Notes

Reaction equation

HRID 1096676 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[C@@H:15]1[CH2:20][CH2:19][CH2:18][NH:17][CH2:16]1.N1CCCCC1.[CH:27]1[C:39]2[CH:38]([CH2:40][O:41][C:42]([NH:44][C@@H:45]3[CH2:49][N:48](C(OC(C)(C)C)=O)[CH2:47][C@H:46]3[C:57](O)=[O:58])=[O:43])[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:31]=2[CH:30]=[CH:29][CH:28]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[C@@H:15]1[CH2:20][CH2:19][CH2:18][N:17]([C:57]([C@@H:46]2[CH2:47][NH:48][CH2:49][C@H:45]2[NH:44][C:42](=[O:43])[O:41][CH2:40][CH:38]2[C:37]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[C:31]3[C:39]2=[CH:27][CH:28]=[CH:29][CH:30]=3)=[O:58])[CH2:16]1

Participants

4

Reactant 3

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 10026865(3R,4S)-1-(tert-Butoxycarbonyl)-4-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)pyrrolidine-3-carboxylic acidHCID 66786519HCID 66786519, compound

Product 1

HCID 66785824HCID 66785824, compound

Procedure

(R)-1-(3-methoxypropyl)-2-(piperidin-3-yl)-1H-benzo[d]imidazole (138C) (3.02 g) was coupled to (3R,4S)-4-(((9H-fluoren-9-yl)methoxy)carbonylamino)-1-(tert-butoxycarbonyl)pyrrolidine-3-carboxylic acid (5 g) (138B) using the standard BOP coupling procedure from Example 138, Step C, Procedure B. The deprotection was performed according to standard procedures (TFA/CH2Cl2; evapn; EtOAc/satd NaHCO3; dry; evapn.) to yield the free amine, (9H-fluoren-9-yl)methyl (3S,4R)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidine-1-carbonyl)pyrrolidin-3-ylcarbamate (139E): ESI-MS: m/z 608.6 (MH+). 1H NMR (400 MHz, MeOH-d4) δ ppm 1.66 (m, 1H) 1.7-2.3 (m, 5H) 4.21-4.25 (m, 2H) 7.1-7.6 (m, 8H). HPLC retention time, T=0.817 min, STDTFA-2 method.

Workup

  1. dry with materialThe deprotection was performed according to standard procedures (TFA/CH2Cl2; evapn; EtOAc/satd NaHCO3; dry; evapn.)

Sources & evidence

ORD record
ord-5b3cd8580d384aaa84919f599c406fda
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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