1-Hydroxybenzotriazole → HCID 58327208, compound

HRID 879879Notes

Reaction equation

HRID 879879 reaction equation
[CH3:1][C:2]1[O:3][C:4]([CH3:10])=[C:5]([C:7]([OH:9])=O)[N:6]=1.C1C=CC2N(O)N=NC=2C=1.Cl.Cl.C[O:24][C:25](=[O:72])[C@@H:26]([NH:42][C:43]([C@@H:45]1[CH2:54][C:53]2[CH:52]=[C:51]3[O:55][CH2:56][C@H:57]([C:59]4[CH:64]=[CH:63][CH:62]=[C:61]([O:65][CH2:66][CH:67]5[CH2:71][CH2:70][CH2:69][CH2:68]5)[CH:60]=4)[O:58][C:50]3=[CH:49][C:48]=2[CH2:47][NH:46]1)=[O:44])[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[CH:39]=[CH:38][N:37]=[C:36]([CH3:40])[C:35]=2[CH3:41])=[CH:30][CH:29]=1.CCN(C(C)C)C(C)C>C(Cl)Cl.CCN=C=NCCCN(C)C.Cl.CCOC(C)=O.CO>[CH:67]1([CH2:66][O:65][C:61]2[CH:60]=[C:59]([C@H:57]3[CH2:56][O:55][C:51]4=[CH:52][C:53]5[CH2:54][C@@H:45]([C:43]([NH:42][C@@H:26]([CH2:27][C:28]6[CH:33]=[CH:32][C:31]([C:34]7[CH:39]=[CH:38][N:37]=[C:36]([CH3:40])[C:35]=7[CH3:41])=[CH:30][CH:29]=6)[C:25]([OH:72])=[O:24])=[O:44])[N:46]([C:7]([C:5]6[N:6]=[C:2]([CH3:1])[O:3][C:4]=6[CH3:10])=[O:9])[CH2:47][C:48]=5[CH:49]=[C:50]4[O:58]3)[CH:64]=[CH:63][CH:62]=2)[CH2:71][CH2:70][CH2:69][CH2:68]1

Participants

9

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27954652,5-Dimethyl-1,3-oxazole-4-carboxylic acidHCID 66719538HCID 66719538, compound

Product 1

HCID 58327208HCID 58327208, compoundYield 69.4%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideSolvent

Conditions

Temperature
0 °C

Procedure

2,5-Dimethyl-oxazole-4-carboxylic acid (6 mg) was taken in 1 mL of anhydrous DCM and EDCl (9 mg), HOBT (7 mg) and (S)-2-{[(3S,8S)-3-(3-cyclopentylmethoxy-phenyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester dihydrochloride (22 mg) and stirred for 5 minutes. The reaction mixture was cooled to 0° C. and DIEA (25 mg) was added and reaction was stirred at room temperature for 2 hours. After the reaction completed, the reaction mixture was loaded onto a silica gel column (1:3 EtOAc:hexanes to 4% MeOH in 1:1 EtOAc:hexanes) to get purified (S)-2-{[(3S,8S)-3-(3-cyclopentylmethoxy-phenyl)-7-(2,5-dimethyl-oxazole-4-carbonyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester (20 mg). This was hydrolyzed according to General Procedure B to get the title compound (16 mg). LCMS (m/z): 786.

Workup

  1. customreaction
  2. customto get
  3. custompurified (S)-2-{[(3S,8S)-3-(3-cyclopentylmethoxy-phenyl)-7-(2,5-dimethyl-oxazole-4-carbonyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester (20 mg)

Sources & evidence

ORD record
ord-ed9fc8270d8d4a29945f107626a4f272
Source dataset
uspto-grants-2015_03
Patent number
US08987295B2

Reaction notes

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