HCID 67045062, compound → HCID 59129492, compound

HRID 1991844Notes

Reaction equation

HRID 1991844 reaction equation
[NH2:1][CH2:2][C@@H:3]([OH:35])[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([NH:14][C:15]([C:17]3([C:20]4[CH:30]=[CH:29][C:23]5[O:24][C:25]([F:28])([F:27])[O:26][C:22]=5[CH:21]=4)[CH2:19][CH2:18]3)=[O:16])=[CH:11][CH:12]=2)[CH:7]=[C:6]1[C:31]([CH3:34])([CH3:33])[CH3:32]>CO.C(N(CC)CC)C>[C:31]([C:6]1[N:5]([CH2:4][C@@H:3]([OH:35])[CH2:2][NH:1][C:25](=[O:26])[O:24][CH3:23])[C:13]2[C:8]([CH:7]=1)=[CH:9][C:10]([NH:14][C:15]([C:17]1([C:20]3[CH:30]=[CH:29][C:23]4[O:24][C:25]([F:28])([F:27])[O:26][C:22]=4[CH:21]=3)[CH2:19][CH2:18]1)=[O:16])=[CH:11][CH:12]=2)([CH3:32])([CH3:34])[CH3:33]

Participants

4

Reactant 1

HCID 67045062HCID 67045062, compound

Product 1

HCID 59129492HCID 59129492, compound

Reagents, catalysts & solvents 2

HCID 8471TriethylamineCatalystHCID 887MethanolSolvent

Procedure

To a stirred solution (R)—N-(1-(3-amino-2-hydroxypropyl)-2-tert-butyl-1H-indol-5-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (0.10 g, 0.20 mmol) in methanol (1 mL) was added 2 drops of triethylamine and methylchloroformyl chloride (0.020 mL, 0.25 mmol). After 30 min, the reaction mixture was filtered and purified using reverse phase HPLC providing (S)-methyl 3-(2-tert-butyl-5-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclo-propanecarboxamido)-1H-indol-1-yl)-2-hydroxypropylcarbamate. The retention time on a three minute run is 1.40 min. LC/MS (M+1)=544.3. 1H NMR (400 MHz, CDCl3) δ 7.52 (d, 1H, J=2 Hz), 7.30 (dd, 1H, J=2, 8 Hz), 7.28 (m, 1H), 7.22 (d, 1H, J=8 Hz), 7.14 (d, 1H, J=8 Hz), 7.04 (br s, 1H), 6.97 (dd, 1H, J=2, 8 Hz), 6.24 (s, 1H), 5.19 (1H, br s), 4.31 (dd, 1H, J=6, 15 Hz), 4.28 (dd, 1H, J=11, 15 Hz), 4.18 (m, 1H), 3.70 (s, 3H), 3.40 (dd, 1H, J=3, 6 Hz), 3.36 (dd, 1H, J=3, 6 Hz), 3.26 (m, 1H), 1.74 (m, 2H), 1.40 (s, 9H), 1.11 (m, 2H).

Workup

  1. filtrationthe reaction mixture was filtered
  2. custompurified

Sources & evidence

ORD record
ord-8e321d4707a4477d8c1c5227af6d5f88
Source dataset
uspto-grants-2010_01
Patent number
US07645789B2

Reaction notes

Loading…