HCID 67045062, compound → HCID 59129492, compound

HRID 2038087Notes

Reaction equation

HRID 2038087 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 mM. LC/MS (M+1)=544.3. 1 H 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, 9 H), 1.11(m, 2 H).

Workup

  1. filtrationthe reaction mixture was filtered
  2. custompurified

Sources & evidence

ORD record
ord-f077cddd57cb480788d90d1a645eab96
Source dataset
uspto-grants-2013_11
Patent number
US08575209B2

Reaction notes

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